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Gene Information
Gene symbol: DPP4
Gene name: dipeptidyl-peptidase 4
HGNC ID: 3009
Synonyms: DPPIV
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 7544802 | Since capillary endothelial cell CD36 expression appeared to correlate with parenchymal cell fatty acid utilization and since CD26 has been identified recently as a long-chain fatty acid-binding protein, we examined heart tissue CD36 expression in murine models of insulin-dependent (nonobese diabetic, NOD) and non-insulin-dependent diabetes mellitus (KKAY). |
| 2 | 9519708 | GLP-1 lowers blood glucose in both NIDDM and IDDM patients and may be therapeutically useful for treatment of patients with diabetes. |
| 3 | 9519708 | GLP-1 regulates blood glucose via stimulation of glucose-dependent insulin secretion, inhibition of gastric emptying, and inhibition of glucagon secretion. |
| 4 | 9519708 | The short duration of action of GLP-1 may be accounted for in part by the enzyme dipeptidyl peptidase 4 (DPP-IV), which cleaves GLP-1 at the NH2-terminus; hence GLP-1 analogs or the lizard peptide exendin-4 that are resistant to DPP-IV cleavage may be more potent GLP-1 molecules in vivo. |
| 5 | 9792533 | The insulinotropic hormone, glucagon-like peptide 1 (GLP-1), which has been proposed as a new treatment for type 2 diabetes, is metabolized extremely rapidly by the ubiquitous enzyme, dipeptidyl peptidase IV (DPP-IV), resulting in the formation of a metabolite, which may act as an antagonist at the GLP-1 receptor. |
| 6 | 9792533 | To exploit the therapeutic potential of GLP-1 clinically, we here propose the use of specific inhibitors of DPP-IV. |
| 7 | 9792533 | GLP-1 has multifaceted actions, which include stimulation of insulin gene expression, trophic effects on the beta-cells, inhibition of glucagon secretion, promotion of satiety, inhibition of food intake, and slowing of gastric emptying, all of which contribute to normalizing elevated glucose levels. |
| 8 | 9792533 | Because of this, we predict that inhibition of DPP-IV, which will elevate the levels of active GLP-1 and reduce the levels of the antagonistic metabolite, may be useful to treat impaired glucose tolerance and perhaps prevent transition to type 2 diabetes. |
| 9 | 9792533 | The actions of DPP-IV, other than degradation of GLP-1, particularly in the immune system are discussed, but it is concluded that side effects of inhibition therapy are likely to be mild. |
| 10 | 9792533 | The insulinotropic hormone, glucagon-like peptide 1 (GLP-1), which has been proposed as a new treatment for type 2 diabetes, is metabolized extremely rapidly by the ubiquitous enzyme, dipeptidyl peptidase IV (DPP-IV), resulting in the formation of a metabolite, which may act as an antagonist at the GLP-1 receptor. |
| 11 | 9792533 | To exploit the therapeutic potential of GLP-1 clinically, we here propose the use of specific inhibitors of DPP-IV. |
| 12 | 9792533 | GLP-1 has multifaceted actions, which include stimulation of insulin gene expression, trophic effects on the beta-cells, inhibition of glucagon secretion, promotion of satiety, inhibition of food intake, and slowing of gastric emptying, all of which contribute to normalizing elevated glucose levels. |
| 13 | 9792533 | Because of this, we predict that inhibition of DPP-IV, which will elevate the levels of active GLP-1 and reduce the levels of the antagonistic metabolite, may be useful to treat impaired glucose tolerance and perhaps prevent transition to type 2 diabetes. |
| 14 | 9792533 | The actions of DPP-IV, other than degradation of GLP-1, particularly in the immune system are discussed, but it is concluded that side effects of inhibition therapy are likely to be mild. |
| 15 | 9792533 | The insulinotropic hormone, glucagon-like peptide 1 (GLP-1), which has been proposed as a new treatment for type 2 diabetes, is metabolized extremely rapidly by the ubiquitous enzyme, dipeptidyl peptidase IV (DPP-IV), resulting in the formation of a metabolite, which may act as an antagonist at the GLP-1 receptor. |
| 16 | 9792533 | To exploit the therapeutic potential of GLP-1 clinically, we here propose the use of specific inhibitors of DPP-IV. |
| 17 | 9792533 | GLP-1 has multifaceted actions, which include stimulation of insulin gene expression, trophic effects on the beta-cells, inhibition of glucagon secretion, promotion of satiety, inhibition of food intake, and slowing of gastric emptying, all of which contribute to normalizing elevated glucose levels. |
| 18 | 9792533 | Because of this, we predict that inhibition of DPP-IV, which will elevate the levels of active GLP-1 and reduce the levels of the antagonistic metabolite, may be useful to treat impaired glucose tolerance and perhaps prevent transition to type 2 diabetes. |
| 19 | 9792533 | The actions of DPP-IV, other than degradation of GLP-1, particularly in the immune system are discussed, but it is concluded that side effects of inhibition therapy are likely to be mild. |
| 20 | 9792533 | The insulinotropic hormone, glucagon-like peptide 1 (GLP-1), which has been proposed as a new treatment for type 2 diabetes, is metabolized extremely rapidly by the ubiquitous enzyme, dipeptidyl peptidase IV (DPP-IV), resulting in the formation of a metabolite, which may act as an antagonist at the GLP-1 receptor. |
| 21 | 9792533 | To exploit the therapeutic potential of GLP-1 clinically, we here propose the use of specific inhibitors of DPP-IV. |
| 22 | 9792533 | GLP-1 has multifaceted actions, which include stimulation of insulin gene expression, trophic effects on the beta-cells, inhibition of glucagon secretion, promotion of satiety, inhibition of food intake, and slowing of gastric emptying, all of which contribute to normalizing elevated glucose levels. |
| 23 | 9792533 | Because of this, we predict that inhibition of DPP-IV, which will elevate the levels of active GLP-1 and reduce the levels of the antagonistic metabolite, may be useful to treat impaired glucose tolerance and perhaps prevent transition to type 2 diabetes. |
| 24 | 9792533 | The actions of DPP-IV, other than degradation of GLP-1, particularly in the immune system are discussed, but it is concluded that side effects of inhibition therapy are likely to be mild. |
| 25 | 10024091 | Recently, it was reported that GLP-1 became resistant to DPPIV when the alanine residue at position 8 was replaced by a glycine (GLP-1-Gly8). |
| 26 | 10024091 | We report here that this change slightly decreased the affinity of the peptide for its receptor (IC50, 0.41 +/- 0.14 and 1.39 +/- 0.61 nmol/L for GLP-1 and GLP-1-Gly8, respectively) but did not change the efficiency to stimulate accumulation of intracellular cyclic adenosine monophosphate (cAMP) (EC50, 0.25 +/- 0.05 and 0.36 +/- 0.06 nmol/L for GLP-1 and GLP-1-Gly8, respectively). |
| 27 | 10823914 | Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. |
| 28 | 10823914 | This enzyme activity has been implicated in the regulation of the biological activity of multiple hormones and chemokines, including the insulinotropic peptides glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). |
| 29 | 10823914 | Levels of glucose-stimulated circulating insulin and the intact insulinotropic form of GLP-1 are increased in CD26(-/-) mice. |
| 30 | 10823914 | This inhibitor also improved glucose tolerance in GLP-1 receptor(-/-) mice, indicating that CD26 contributes to blood glucose regulation by controlling the activity of GLP-1 as well as additional substrates. |
| 31 | 10823914 | Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. |
| 32 | 10823914 | This enzyme activity has been implicated in the regulation of the biological activity of multiple hormones and chemokines, including the insulinotropic peptides glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). |
| 33 | 10823914 | Levels of glucose-stimulated circulating insulin and the intact insulinotropic form of GLP-1 are increased in CD26(-/-) mice. |
| 34 | 10823914 | This inhibitor also improved glucose tolerance in GLP-1 receptor(-/-) mice, indicating that CD26 contributes to blood glucose regulation by controlling the activity of GLP-1 as well as additional substrates. |
| 35 | 10823914 | Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. |
| 36 | 10823914 | This enzyme activity has been implicated in the regulation of the biological activity of multiple hormones and chemokines, including the insulinotropic peptides glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). |
| 37 | 10823914 | Levels of glucose-stimulated circulating insulin and the intact insulinotropic form of GLP-1 are increased in CD26(-/-) mice. |
| 38 | 10823914 | This inhibitor also improved glucose tolerance in GLP-1 receptor(-/-) mice, indicating that CD26 contributes to blood glucose regulation by controlling the activity of GLP-1 as well as additional substrates. |
| 39 | 11284388 | In addition to, but independent of its serine type catalytic activity, DPPIV binds closely to the soluble extracellular enzyme adenosine deaminase. |
| 40 | 11284388 | Other known substrates which are subject in vitro to receptor-specific changes induced by DPPIV truncation include neuropeptides such as substance P, peptidE YY and neuropeptide Y. |
| 41 | 11284388 | On the other hand, DPPIV mediated cleavage of the N-terminal His-Ala or Tyr-Ala dipeptides from circulating incretin hormones like, glucagon-like peptides (GLP)-1 and -2, gastric inhibitory polypeptide (GIP), all members of the enteroglucagon/GRF superfamily, results in their biological inactivation in vitro and in vivo. |
| 42 | 11284388 | Administration of specific DPPIV inhibitors closes this pathway of incretin degradation and greatly enhances insulin secretion. |
| 43 | 11284388 | In addition to, but independent of its serine type catalytic activity, DPPIV binds closely to the soluble extracellular enzyme adenosine deaminase. |
| 44 | 11284388 | Other known substrates which are subject in vitro to receptor-specific changes induced by DPPIV truncation include neuropeptides such as substance P, peptidE YY and neuropeptide Y. |
| 45 | 11284388 | On the other hand, DPPIV mediated cleavage of the N-terminal His-Ala or Tyr-Ala dipeptides from circulating incretin hormones like, glucagon-like peptides (GLP)-1 and -2, gastric inhibitory polypeptide (GIP), all members of the enteroglucagon/GRF superfamily, results in their biological inactivation in vitro and in vivo. |
| 46 | 11284388 | Administration of specific DPPIV inhibitors closes this pathway of incretin degradation and greatly enhances insulin secretion. |
| 47 | 11284388 | In addition to, but independent of its serine type catalytic activity, DPPIV binds closely to the soluble extracellular enzyme adenosine deaminase. |
| 48 | 11284388 | Other known substrates which are subject in vitro to receptor-specific changes induced by DPPIV truncation include neuropeptides such as substance P, peptidE YY and neuropeptide Y. |
| 49 | 11284388 | On the other hand, DPPIV mediated cleavage of the N-terminal His-Ala or Tyr-Ala dipeptides from circulating incretin hormones like, glucagon-like peptides (GLP)-1 and -2, gastric inhibitory polypeptide (GIP), all members of the enteroglucagon/GRF superfamily, results in their biological inactivation in vitro and in vivo. |
| 50 | 11284388 | Administration of specific DPPIV inhibitors closes this pathway of incretin degradation and greatly enhances insulin secretion. |
| 51 | 11284388 | In addition to, but independent of its serine type catalytic activity, DPPIV binds closely to the soluble extracellular enzyme adenosine deaminase. |
| 52 | 11284388 | Other known substrates which are subject in vitro to receptor-specific changes induced by DPPIV truncation include neuropeptides such as substance P, peptidE YY and neuropeptide Y. |
| 53 | 11284388 | On the other hand, DPPIV mediated cleavage of the N-terminal His-Ala or Tyr-Ala dipeptides from circulating incretin hormones like, glucagon-like peptides (GLP)-1 and -2, gastric inhibitory polypeptide (GIP), all members of the enteroglucagon/GRF superfamily, results in their biological inactivation in vitro and in vivo. |
| 54 | 11284388 | Administration of specific DPPIV inhibitors closes this pathway of incretin degradation and greatly enhances insulin secretion. |
| 55 | 11460578 | Of the known gut hormones only gastric inhibitory polypeptide (GIP) and glucagon-like polypeptide-1 (GLP-1 [7-36] amide) fulfill this definition. |
| 56 | 11460578 | --The incretin effect (i.e. the ratio between the integrated insulin response to an oral glucose load and an isoglycaemic intravenous glucose infusion) is markedly diminished in patients with type 2 diabetes mellitus, while the plasma levels of GIP and GLP-1 and their responses to nutrients are in the normal range. |
| 57 | 11460578 | This insensitivity of the diabetic B-cells towards incretins can be overcome by supraphysiological (pharmacological) concentrations of GLP-1 [7-36], however not of GIP. |
| 58 | 11460578 | At present methods are being developed to improve the pharmacokinetics of GLP-1 by inhibition of the cleaving enzyme dipeptidyl peptidase IV (DPP-IV) or by synthesis of DPP-IV resistant GLP-1 analogues. |
| 59 | 11978643 | Acute suppression of dipeptidyl peptidase IV (DPP-IV) activity improves glucose tolerance in the Zucker fatty rat, a rodent model of impaired glucose tolerance, through stabilization of glucagon-like peptide (GLP)-1. |
| 60 | 11991725 | A large genomic tandem duplication event that included DPP4-like and GCG genes occurred before the amphibian-mammal divergence, but one of the duplicated copies of GCG has been lost on the human lineage. |
| 61 | 11991725 | Recently, a processed pseudogene of the X-chromosome-linked gene TIMM8A was inserted downstream of GCG. |
| 62 | 12393301 | This article reviews recent developments in research on several of these targets, namely acetyl-CoA carboxylase 2 (ACC2), I kappa kinase (IKK) beta, dipeptidyl peptidase IV (DPP-IV) and glucagon-like peptide-1 receptor (GLP-1R). |
| 63 | 12419322 | There are two possible mechanisms for this effect: (1) metformin inhibits dipeptidyl peptidase IV (DPPIV), an enzyme degrading GLP-1, and (2) metformin enhances GLP-1 secretion. |
| 64 | 12419322 | To elucidate the mechanism(s), we examined (1) IC(50) of metformin for DPPIV inhibition, (2) plasma active GLP-1 changes after oral biguanide (metformin, phenformin, and buformin) treatment in fasting DPPIV-deficient F344/DuCrj rats, and (3) plasma intact GLP-1 excursions after oral administration of metformin and/or valine-pyrrolidide, a DPPIV inhibitor, in fasting DPPIV-positive F344/Jcl rats. |
| 65 | 12419322 | Metformin treatment (30, 100, and 300mg/kg) increased plasma active GLP-1 levels dose-dependently in DPPIV-deficient F344/DuCrj rats (approximately 1.6-fold at 3 and 5h after administration of 300mg/kg). |
| 66 | 12419322 | In DPPIV-positive F344/Jcl rats, coadministration of metformin (300mg/kg) and valine-pyrrolidide (30mg/kg) resulted in elevation of plasma active GLP-1, but neither metformin nor valine-pyrrolidide treatment alone had any effect. |
| 67 | 12419322 | These findings suggest that metformin has no direct inhibitory effect on DPPIV activity and that metformin and the other biguanides enhance GLP-1 secretion, without altering glucose metabolism. |
| 68 | 12419322 | There are two possible mechanisms for this effect: (1) metformin inhibits dipeptidyl peptidase IV (DPPIV), an enzyme degrading GLP-1, and (2) metformin enhances GLP-1 secretion. |
| 69 | 12419322 | To elucidate the mechanism(s), we examined (1) IC(50) of metformin for DPPIV inhibition, (2) plasma active GLP-1 changes after oral biguanide (metformin, phenformin, and buformin) treatment in fasting DPPIV-deficient F344/DuCrj rats, and (3) plasma intact GLP-1 excursions after oral administration of metformin and/or valine-pyrrolidide, a DPPIV inhibitor, in fasting DPPIV-positive F344/Jcl rats. |
| 70 | 12419322 | Metformin treatment (30, 100, and 300mg/kg) increased plasma active GLP-1 levels dose-dependently in DPPIV-deficient F344/DuCrj rats (approximately 1.6-fold at 3 and 5h after administration of 300mg/kg). |
| 71 | 12419322 | In DPPIV-positive F344/Jcl rats, coadministration of metformin (300mg/kg) and valine-pyrrolidide (30mg/kg) resulted in elevation of plasma active GLP-1, but neither metformin nor valine-pyrrolidide treatment alone had any effect. |
| 72 | 12419322 | These findings suggest that metformin has no direct inhibitory effect on DPPIV activity and that metformin and the other biguanides enhance GLP-1 secretion, without altering glucose metabolism. |
| 73 | 12419322 | There are two possible mechanisms for this effect: (1) metformin inhibits dipeptidyl peptidase IV (DPPIV), an enzyme degrading GLP-1, and (2) metformin enhances GLP-1 secretion. |
| 74 | 12419322 | To elucidate the mechanism(s), we examined (1) IC(50) of metformin for DPPIV inhibition, (2) plasma active GLP-1 changes after oral biguanide (metformin, phenformin, and buformin) treatment in fasting DPPIV-deficient F344/DuCrj rats, and (3) plasma intact GLP-1 excursions after oral administration of metformin and/or valine-pyrrolidide, a DPPIV inhibitor, in fasting DPPIV-positive F344/Jcl rats. |
| 75 | 12419322 | Metformin treatment (30, 100, and 300mg/kg) increased plasma active GLP-1 levels dose-dependently in DPPIV-deficient F344/DuCrj rats (approximately 1.6-fold at 3 and 5h after administration of 300mg/kg). |
| 76 | 12419322 | In DPPIV-positive F344/Jcl rats, coadministration of metformin (300mg/kg) and valine-pyrrolidide (30mg/kg) resulted in elevation of plasma active GLP-1, but neither metformin nor valine-pyrrolidide treatment alone had any effect. |
| 77 | 12419322 | These findings suggest that metformin has no direct inhibitory effect on DPPIV activity and that metformin and the other biguanides enhance GLP-1 secretion, without altering glucose metabolism. |
| 78 | 12419322 | There are two possible mechanisms for this effect: (1) metformin inhibits dipeptidyl peptidase IV (DPPIV), an enzyme degrading GLP-1, and (2) metformin enhances GLP-1 secretion. |
| 79 | 12419322 | To elucidate the mechanism(s), we examined (1) IC(50) of metformin for DPPIV inhibition, (2) plasma active GLP-1 changes after oral biguanide (metformin, phenformin, and buformin) treatment in fasting DPPIV-deficient F344/DuCrj rats, and (3) plasma intact GLP-1 excursions after oral administration of metformin and/or valine-pyrrolidide, a DPPIV inhibitor, in fasting DPPIV-positive F344/Jcl rats. |
| 80 | 12419322 | Metformin treatment (30, 100, and 300mg/kg) increased plasma active GLP-1 levels dose-dependently in DPPIV-deficient F344/DuCrj rats (approximately 1.6-fold at 3 and 5h after administration of 300mg/kg). |
| 81 | 12419322 | In DPPIV-positive F344/Jcl rats, coadministration of metformin (300mg/kg) and valine-pyrrolidide (30mg/kg) resulted in elevation of plasma active GLP-1, but neither metformin nor valine-pyrrolidide treatment alone had any effect. |
| 82 | 12419322 | These findings suggest that metformin has no direct inhibitory effect on DPPIV activity and that metformin and the other biguanides enhance GLP-1 secretion, without altering glucose metabolism. |
| 83 | 12419322 | There are two possible mechanisms for this effect: (1) metformin inhibits dipeptidyl peptidase IV (DPPIV), an enzyme degrading GLP-1, and (2) metformin enhances GLP-1 secretion. |
| 84 | 12419322 | To elucidate the mechanism(s), we examined (1) IC(50) of metformin for DPPIV inhibition, (2) plasma active GLP-1 changes after oral biguanide (metformin, phenformin, and buformin) treatment in fasting DPPIV-deficient F344/DuCrj rats, and (3) plasma intact GLP-1 excursions after oral administration of metformin and/or valine-pyrrolidide, a DPPIV inhibitor, in fasting DPPIV-positive F344/Jcl rats. |
| 85 | 12419322 | Metformin treatment (30, 100, and 300mg/kg) increased plasma active GLP-1 levels dose-dependently in DPPIV-deficient F344/DuCrj rats (approximately 1.6-fold at 3 and 5h after administration of 300mg/kg). |
| 86 | 12419322 | In DPPIV-positive F344/Jcl rats, coadministration of metformin (300mg/kg) and valine-pyrrolidide (30mg/kg) resulted in elevation of plasma active GLP-1, but neither metformin nor valine-pyrrolidide treatment alone had any effect. |
| 87 | 12419322 | These findings suggest that metformin has no direct inhibitory effect on DPPIV activity and that metformin and the other biguanides enhance GLP-1 secretion, without altering glucose metabolism. |
| 88 | 12517256 | Incretins are peptide hormones, exemplified by glucose-dependent insulinotropic peptide and glucagon-like peptide 1 that are released from the gut in response to nutrient ingestion and enhance glucose-stimulated insulin secretion. |
| 89 | 12517256 | Hence, inhibition of glucose-dependent insulinotropic peptide and glucagon-like peptide 1 degradation via reduction of DPP-IV activity represents an innovative strategy for enhancing incretin action in vivo. |
| 90 | 12524666 | However, GLP-1 is rapidly degraded by dipeptidyl peptidase IV (DPPIV) after its release. |
| 91 | 12524666 | In this study, using C57BLKS/J-db/db (db/db) mice as a model of type 2 diabetes, we examined the effect of acute DPPIV inhibition on glucose tolerance at the early and later stages of diabetes, determining plasma active GLP-1 and insulin levels. |
| 92 | 12524666 | The administration of valine-pyrrolidide, a DPPIV inhibitor, resulted in potentiated insulin secretion mediated by increased endogenous GLP-1 action, leading to improved glucose tolerance in db/db mice at 6 weeks of age. |
| 93 | 12524666 | However, although acute DPPIV inhibition with valine-pyrrolidide resulted in higher plasma active GLP-1 and insulin levels in db/db mice at 23 weeks of age, it did not improve glucose tolerance. |
| 94 | 12524666 | The function of the enteroinsular axis is preserved in both stage of diabetes and the DPPIV inhibitor potentiated it, but the progression of insulin resistance appeared to block the improvement of glucose tolerance through DPPIV inhibition. |
| 95 | 12524666 | However, GLP-1 is rapidly degraded by dipeptidyl peptidase IV (DPPIV) after its release. |
| 96 | 12524666 | In this study, using C57BLKS/J-db/db (db/db) mice as a model of type 2 diabetes, we examined the effect of acute DPPIV inhibition on glucose tolerance at the early and later stages of diabetes, determining plasma active GLP-1 and insulin levels. |
| 97 | 12524666 | The administration of valine-pyrrolidide, a DPPIV inhibitor, resulted in potentiated insulin secretion mediated by increased endogenous GLP-1 action, leading to improved glucose tolerance in db/db mice at 6 weeks of age. |
| 98 | 12524666 | However, although acute DPPIV inhibition with valine-pyrrolidide resulted in higher plasma active GLP-1 and insulin levels in db/db mice at 23 weeks of age, it did not improve glucose tolerance. |
| 99 | 12524666 | The function of the enteroinsular axis is preserved in both stage of diabetes and the DPPIV inhibitor potentiated it, but the progression of insulin resistance appeared to block the improvement of glucose tolerance through DPPIV inhibition. |
| 100 | 12524666 | However, GLP-1 is rapidly degraded by dipeptidyl peptidase IV (DPPIV) after its release. |
| 101 | 12524666 | In this study, using C57BLKS/J-db/db (db/db) mice as a model of type 2 diabetes, we examined the effect of acute DPPIV inhibition on glucose tolerance at the early and later stages of diabetes, determining plasma active GLP-1 and insulin levels. |
| 102 | 12524666 | The administration of valine-pyrrolidide, a DPPIV inhibitor, resulted in potentiated insulin secretion mediated by increased endogenous GLP-1 action, leading to improved glucose tolerance in db/db mice at 6 weeks of age. |
| 103 | 12524666 | However, although acute DPPIV inhibition with valine-pyrrolidide resulted in higher plasma active GLP-1 and insulin levels in db/db mice at 23 weeks of age, it did not improve glucose tolerance. |
| 104 | 12524666 | The function of the enteroinsular axis is preserved in both stage of diabetes and the DPPIV inhibitor potentiated it, but the progression of insulin resistance appeared to block the improvement of glucose tolerance through DPPIV inhibition. |
| 105 | 12524666 | However, GLP-1 is rapidly degraded by dipeptidyl peptidase IV (DPPIV) after its release. |
| 106 | 12524666 | In this study, using C57BLKS/J-db/db (db/db) mice as a model of type 2 diabetes, we examined the effect of acute DPPIV inhibition on glucose tolerance at the early and later stages of diabetes, determining plasma active GLP-1 and insulin levels. |
| 107 | 12524666 | The administration of valine-pyrrolidide, a DPPIV inhibitor, resulted in potentiated insulin secretion mediated by increased endogenous GLP-1 action, leading to improved glucose tolerance in db/db mice at 6 weeks of age. |
| 108 | 12524666 | However, although acute DPPIV inhibition with valine-pyrrolidide resulted in higher plasma active GLP-1 and insulin levels in db/db mice at 23 weeks of age, it did not improve glucose tolerance. |
| 109 | 12524666 | The function of the enteroinsular axis is preserved in both stage of diabetes and the DPPIV inhibitor potentiated it, but the progression of insulin resistance appeared to block the improvement of glucose tolerance through DPPIV inhibition. |
| 110 | 12524666 | However, GLP-1 is rapidly degraded by dipeptidyl peptidase IV (DPPIV) after its release. |
| 111 | 12524666 | In this study, using C57BLKS/J-db/db (db/db) mice as a model of type 2 diabetes, we examined the effect of acute DPPIV inhibition on glucose tolerance at the early and later stages of diabetes, determining plasma active GLP-1 and insulin levels. |
| 112 | 12524666 | The administration of valine-pyrrolidide, a DPPIV inhibitor, resulted in potentiated insulin secretion mediated by increased endogenous GLP-1 action, leading to improved glucose tolerance in db/db mice at 6 weeks of age. |
| 113 | 12524666 | However, although acute DPPIV inhibition with valine-pyrrolidide resulted in higher plasma active GLP-1 and insulin levels in db/db mice at 23 weeks of age, it did not improve glucose tolerance. |
| 114 | 12524666 | The function of the enteroinsular axis is preserved in both stage of diabetes and the DPPIV inhibitor potentiated it, but the progression of insulin resistance appeared to block the improvement of glucose tolerance through DPPIV inhibition. |
| 115 | 12525257 | The therapeutic potential of glucagon-like peptide-1 (GLP-1) in improving glycaemic control in diabetes has been widely studied, but the potential beneficial effects of glucose-dependent insulinotropic polypeptide (GIP) have until recently been almost overlooked. |
| 116 | 12525257 | One of the major problems, however, in exploiting either GIP or GLP-1 as potential therapeutic agents is their short duration of action, due to enzymatic degradation in vivo by dipeptidylpeptidase IV (DPP IV). |
| 117 | 12525257 | Following incubation in plasma, (Ser2)GIP had a reduced hydrolysis rate compared with native GIP, while (Gly2)GIP was completely stable. |
| 118 | 12525257 | In Chinese hamster lung fibroblasts stably transfected with the human GIP receptor, GIP, (Gly2)GIP and (Ser2)GIP stimulated cAMP production with EC(50) values of 18.2, 14.9 and 15.0 nM respectively. |
| 119 | 12525257 | In the pancreatic BRIN-BD11 beta-cell line, (Gly2)GIP and (Ser2)GIP (10(-8) M) evoked significant increases (1.2- and 1.5-fold respectively; P<0.01 to P<0.001) in insulinotropic activity compared with GIP. |
| 120 | 12525257 | This enhanced glucose-lowering ability was coupled to a significantly raised (P<0.01) and more protracted insulin response compared with GIP. |
| 121 | 12534281 | Dipeptidyl peptidase IV (DP-IV/CD26), fibroblast activation protein (FAP), DP-like 1 (DPL1), DP8, DP9, and DPL2 comprise the CD26 gene family. |
| 122 | 12534281 | DPIV substrates include the glucagonlike peptides, neuropeptide Y, and the chemokines CCL3, CCL5, CCL11, CCL22, and CXCL12. |
| 123 | 12534281 | We have proposed that the extracellular region of CD26 is analogous to prolyl oligopeptidase in consisting of an alpha/beta hydrolase domain contributed by both N- and C-terminal portions of the polypeptide and a seven-blade beta-propeller domain. |
| 124 | 12534281 | Replacing the C-terminal portion of the predicted alpha/beta hydrolase domain of CD26 (residues 501-766) with the homologous portion of DP8 or DP9 produced intact proteins. |
| 125 | 12534281 | Glu(259) of DP8, a residue distant from the catalytic triad yet greatly conserved in the CD26 gene family, was shown to be required for peptidase activity. |
| 126 | 12534281 | These data concord with our predicted CD26 structure, indicate that biosynthesis of a functional fragment of CD26 is difficult, and confirm the functional homology of DP8 with CD26. |
| 127 | 12534281 | Dipeptidyl peptidase IV (DP-IV/CD26), fibroblast activation protein (FAP), DP-like 1 (DPL1), DP8, DP9, and DPL2 comprise the CD26 gene family. |
| 128 | 12534281 | DPIV substrates include the glucagonlike peptides, neuropeptide Y, and the chemokines CCL3, CCL5, CCL11, CCL22, and CXCL12. |
| 129 | 12534281 | We have proposed that the extracellular region of CD26 is analogous to prolyl oligopeptidase in consisting of an alpha/beta hydrolase domain contributed by both N- and C-terminal portions of the polypeptide and a seven-blade beta-propeller domain. |
| 130 | 12534281 | Replacing the C-terminal portion of the predicted alpha/beta hydrolase domain of CD26 (residues 501-766) with the homologous portion of DP8 or DP9 produced intact proteins. |
| 131 | 12534281 | Glu(259) of DP8, a residue distant from the catalytic triad yet greatly conserved in the CD26 gene family, was shown to be required for peptidase activity. |
| 132 | 12534281 | These data concord with our predicted CD26 structure, indicate that biosynthesis of a functional fragment of CD26 is difficult, and confirm the functional homology of DP8 with CD26. |
| 133 | 12534281 | Dipeptidyl peptidase IV (DP-IV/CD26), fibroblast activation protein (FAP), DP-like 1 (DPL1), DP8, DP9, and DPL2 comprise the CD26 gene family. |
| 134 | 12534281 | DPIV substrates include the glucagonlike peptides, neuropeptide Y, and the chemokines CCL3, CCL5, CCL11, CCL22, and CXCL12. |
| 135 | 12534281 | We have proposed that the extracellular region of CD26 is analogous to prolyl oligopeptidase in consisting of an alpha/beta hydrolase domain contributed by both N- and C-terminal portions of the polypeptide and a seven-blade beta-propeller domain. |
| 136 | 12534281 | Replacing the C-terminal portion of the predicted alpha/beta hydrolase domain of CD26 (residues 501-766) with the homologous portion of DP8 or DP9 produced intact proteins. |
| 137 | 12534281 | Glu(259) of DP8, a residue distant from the catalytic triad yet greatly conserved in the CD26 gene family, was shown to be required for peptidase activity. |
| 138 | 12534281 | These data concord with our predicted CD26 structure, indicate that biosynthesis of a functional fragment of CD26 is difficult, and confirm the functional homology of DP8 with CD26. |
| 139 | 12534281 | Dipeptidyl peptidase IV (DP-IV/CD26), fibroblast activation protein (FAP), DP-like 1 (DPL1), DP8, DP9, and DPL2 comprise the CD26 gene family. |
| 140 | 12534281 | DPIV substrates include the glucagonlike peptides, neuropeptide Y, and the chemokines CCL3, CCL5, CCL11, CCL22, and CXCL12. |
| 141 | 12534281 | We have proposed that the extracellular region of CD26 is analogous to prolyl oligopeptidase in consisting of an alpha/beta hydrolase domain contributed by both N- and C-terminal portions of the polypeptide and a seven-blade beta-propeller domain. |
| 142 | 12534281 | Replacing the C-terminal portion of the predicted alpha/beta hydrolase domain of CD26 (residues 501-766) with the homologous portion of DP8 or DP9 produced intact proteins. |
| 143 | 12534281 | Glu(259) of DP8, a residue distant from the catalytic triad yet greatly conserved in the CD26 gene family, was shown to be required for peptidase activity. |
| 144 | 12534281 | These data concord with our predicted CD26 structure, indicate that biosynthesis of a functional fragment of CD26 is difficult, and confirm the functional homology of DP8 with CD26. |
| 145 | 12534281 | Dipeptidyl peptidase IV (DP-IV/CD26), fibroblast activation protein (FAP), DP-like 1 (DPL1), DP8, DP9, and DPL2 comprise the CD26 gene family. |
| 146 | 12534281 | DPIV substrates include the glucagonlike peptides, neuropeptide Y, and the chemokines CCL3, CCL5, CCL11, CCL22, and CXCL12. |
| 147 | 12534281 | We have proposed that the extracellular region of CD26 is analogous to prolyl oligopeptidase in consisting of an alpha/beta hydrolase domain contributed by both N- and C-terminal portions of the polypeptide and a seven-blade beta-propeller domain. |
| 148 | 12534281 | Replacing the C-terminal portion of the predicted alpha/beta hydrolase domain of CD26 (residues 501-766) with the homologous portion of DP8 or DP9 produced intact proteins. |
| 149 | 12534281 | Glu(259) of DP8, a residue distant from the catalytic triad yet greatly conserved in the CD26 gene family, was shown to be required for peptidase activity. |
| 150 | 12534281 | These data concord with our predicted CD26 structure, indicate that biosynthesis of a functional fragment of CD26 is difficult, and confirm the functional homology of DP8 with CD26. |
| 151 | 12606517 | Development and characterization of a glucagon-like peptide 1-albumin conjugate: the ability to activate the glucagon-like peptide 1 receptor in vivo. |
| 152 | 12606517 | The rapid degradation of native glucagon-like peptide 1 (GLP-1) by dipeptidyl peptidase-IV (DPP-IV) has fostered new approaches for generation of degradation-resistant GLP-1 analogues. |
| 153 | 12606517 | We examined the biological activity of CJC-1131, a DPP-IV-resistant drug affinity complex (DAC) GLP-1 compound that conjugates to albumin in vivo. |
| 154 | 12606517 | The CJC-1131 albumin conjugate bound to the GLP-1 receptor (GLP-1R) and activated cAMP formation in heterologous fibroblasts expressing a GLP-1R. |
| 155 | 12606517 | These findings demonstrate that an albumin-conjugated DAC:GLP-1 mimics the action of native GLP-1 and represents a new approach for prolonged activation of GLP-1R signaling. |
| 156 | 12675249 | Implementation of GLP-1 based therapy of type 2 diabetes mellitus using DPP-IV inhibitors. |
| 157 | 12675249 | The mode of action of GLP-1 is complex involving also interactions with sensory neurons and the central nervous system, where a DPP-IV mediated degradation does not seem to occur. |
| 158 | 12675249 | Even the effects of GLP-1 effects on the pancreatic islets may be partly neurally mediated and therefore uninfluenced by DPP-IV inhibition. |
| 159 | 12675249 | Implementation of GLP-1 based therapy of type 2 diabetes mellitus using DPP-IV inhibitors. |
| 160 | 12675249 | The mode of action of GLP-1 is complex involving also interactions with sensory neurons and the central nervous system, where a DPP-IV mediated degradation does not seem to occur. |
| 161 | 12675249 | Even the effects of GLP-1 effects on the pancreatic islets may be partly neurally mediated and therefore uninfluenced by DPP-IV inhibition. |
| 162 | 12675249 | Implementation of GLP-1 based therapy of type 2 diabetes mellitus using DPP-IV inhibitors. |
| 163 | 12675249 | The mode of action of GLP-1 is complex involving also interactions with sensory neurons and the central nervous system, where a DPP-IV mediated degradation does not seem to occur. |
| 164 | 12675249 | Even the effects of GLP-1 effects on the pancreatic islets may be partly neurally mediated and therefore uninfluenced by DPP-IV inhibition. |
| 165 | 12800091 | Degradation, cyclic adenosine monophosphate production, insulin secretion, and glycemic effects of two novel N-terminal Ala2-substituted analogs of glucose-dependent insulinotropic polypeptide with preserved biological activity in vivo. |
| 166 | 12800091 | Glucose-dependent insulinotropic polypeptide (GIP) has significant potential in diabetes therapy due to its ability to serve as a glucose-dependent activator of insulin secretion. |
| 167 | 12800091 | However, its biological activity is severely compromised by the ubiquitous enzyme dipeptidylpeptidase IV (DPP IV), which removes the N-terminal Tyr(1)-Ala(2) dipeptide from GIP. |
| 168 | 12800091 | In Chinese hamster lung (CHL) cells expressing the cloned human GIP receptor, native GIP, (Abu(2))GIP, and (Sar(2))GIP dose-dependently stimulated cyclic adenosine monophosphate (camp) production with EC(50) values of 18.2, 38.5, and 54.6 nmol/L, respectively. |
| 169 | 12800091 | In BRIN-BD11 cells, both (Abu(2))GIP and (Sar(2))GIP (10(-13) to 10(-8) mol/L) dose-dependently stimulated insulin secretion with significantly enhanced effects at 16.7 mmol/L compared with 5.6 mmol/L glucose. |
| 170 | 12800091 | In obese diabetic (ob/ob) mice, GIP and (Sar(2))GIP significantly increased (1.4-fold to 1.5-fold; P <.05) plasma insulin concentrations, whereas (Abu(2))GIP exerted only minor effects. |
| 171 | 12808880 | Glucagon-like peptide-1 (GLP-1 (7-36) amide) is a gut hormone released from L-cells in the small intestine in response to the ingestion of nutrients and enhances the glucose-dependent secretion of insulin from pancreatic beta-cells. |
| 172 | 12808880 | In type 2 diabetic patients, the continuous infusion of GLP-1 (7-36) amide decreases plasma glucose and hemoglobin A1c concentrations and improves beta-cell function. |
| 173 | 12808880 | Hormone action is rapidly terminated by the N-terminal cleavage of GLP-1 at Ala2 by the aminopeptidase, dipeptidyl peptidase IV (DPPIV). |
| 174 | 12808880 | The inhibition of endogenous GLP-1 degradation by reducing DPPIV activity is an alternative strategy for improving the incretin action of GLP-1 in vivo. |
| 175 | 12808880 | Glucagon-like peptide-1 (GLP-1 (7-36) amide) is a gut hormone released from L-cells in the small intestine in response to the ingestion of nutrients and enhances the glucose-dependent secretion of insulin from pancreatic beta-cells. |
| 176 | 12808880 | In type 2 diabetic patients, the continuous infusion of GLP-1 (7-36) amide decreases plasma glucose and hemoglobin A1c concentrations and improves beta-cell function. |
| 177 | 12808880 | Hormone action is rapidly terminated by the N-terminal cleavage of GLP-1 at Ala2 by the aminopeptidase, dipeptidyl peptidase IV (DPPIV). |
| 178 | 12808880 | The inhibition of endogenous GLP-1 degradation by reducing DPPIV activity is an alternative strategy for improving the incretin action of GLP-1 in vivo. |
| 179 | 12892317 | Dipeptidyl-peptidase IV/CD26 (DPP IV) is a cell-surface protease belonging to the prolyloligopeptidase family. |
| 180 | 12892317 | Apart from its catalytic activity, it interacts with several proteins, for instance, adenosine deaminase, the HIV gp120 protein, fibronectin, collagen, the chemokine receptor CXCR4, and the tyrosine phosphatase CD45. |
| 181 | 12892317 | The role of DPP IV/ CD26 within the immune system is a combination of its exopeptidase activity and its interactions with different molecules. |
| 182 | 12892317 | This enables DPP IV/CD26 to serve as a co-stimulatory molecule to influence T cell activity and to modulate chemotaxis. |
| 183 | 12892317 | Dipeptidyl-peptidase IV/CD26 (DPP IV) is a cell-surface protease belonging to the prolyloligopeptidase family. |
| 184 | 12892317 | Apart from its catalytic activity, it interacts with several proteins, for instance, adenosine deaminase, the HIV gp120 protein, fibronectin, collagen, the chemokine receptor CXCR4, and the tyrosine phosphatase CD45. |
| 185 | 12892317 | The role of DPP IV/ CD26 within the immune system is a combination of its exopeptidase activity and its interactions with different molecules. |
| 186 | 12892317 | This enables DPP IV/CD26 to serve as a co-stimulatory molecule to influence T cell activity and to modulate chemotaxis. |
| 187 | 12892317 | Dipeptidyl-peptidase IV/CD26 (DPP IV) is a cell-surface protease belonging to the prolyloligopeptidase family. |
| 188 | 12892317 | Apart from its catalytic activity, it interacts with several proteins, for instance, adenosine deaminase, the HIV gp120 protein, fibronectin, collagen, the chemokine receptor CXCR4, and the tyrosine phosphatase CD45. |
| 189 | 12892317 | The role of DPP IV/ CD26 within the immune system is a combination of its exopeptidase activity and its interactions with different molecules. |
| 190 | 12892317 | This enables DPP IV/CD26 to serve as a co-stimulatory molecule to influence T cell activity and to modulate chemotaxis. |
| 191 | 12901855 | Glucose-dependent insulinotropic polypeptide (GIP) is a key incretin hormone, released postprandially into the circulation in response to feeding, producing a glucose-dependent stimulation of insulin secretion. |
| 192 | 12901855 | A major drawback to achieving this goal has been the rapid degradation of circulating GIP by the ubiquitous enzyme, dipeptidylpeptidase IV (DPP IV). |
| 193 | 12906826 | Inhibition of dipeptidyl peptidase IV (DPP-IV), the main glucagon-like peptide 1 (GLP1)-degrading enzyme, has been proposed for the treatment of type II diabetes. |
| 194 | 12941425 | This class includes dipeptidyl peptidase IV (DPP IV; also termed CD26), fibroblast activation protein alpha (FAP; seprase), DPP7 (DPP II; quiescent cell proline dipeptidase), DPP8, DPP9, and prolyl carboxypeptidase (PCP; angiotensinase C). |
| 195 | 12941425 | More distant members include prolyl oligopeptidase (POP; post proline cleaving enzyme) and acylaminoacylpeptidase (AAP; acylpeptide hydrolase). |
| 196 | 12975025 | In humans, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the most important incretins. |
| 197 | 12975025 | This has been most successful for GLP-1, which exerts antidiabetogenic properties in subjects with type 2 diabetes by stimulating insulin secretion, increasing beta-cell mass, inhibiting glucagon secretion, delaying gastric emptying, and inducing satiety. |
| 198 | 12975025 | However, GLP-1 is rapidly degraded by the enzyme dipeptidyl peptidase IV (DPPIV), making it unattractive as a therapeutic agent because of a very short half-life. |
| 199 | 12975025 | Successful strategies to overcome this difficulty are the use of DPPIV-resistant GLP-1 receptor agonists, such as NN2211 or exendin-4, and the use of inhibitors of DPPIV, such as NVPDPP728 and P32/98. |
| 200 | 12975025 | In humans, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the most important incretins. |
| 201 | 12975025 | This has been most successful for GLP-1, which exerts antidiabetogenic properties in subjects with type 2 diabetes by stimulating insulin secretion, increasing beta-cell mass, inhibiting glucagon secretion, delaying gastric emptying, and inducing satiety. |
| 202 | 12975025 | However, GLP-1 is rapidly degraded by the enzyme dipeptidyl peptidase IV (DPPIV), making it unattractive as a therapeutic agent because of a very short half-life. |
| 203 | 12975025 | Successful strategies to overcome this difficulty are the use of DPPIV-resistant GLP-1 receptor agonists, such as NN2211 or exendin-4, and the use of inhibitors of DPPIV, such as NVPDPP728 and P32/98. |
| 204 | 14582447 | Of the 19 documents that are analyzed in depth in this review, two related to renal cell carcinoma, three each to diabetic nephropathy, renal failure and/or allograft preservation or fibrosis, and four to inhibitors of angiotensin-converting enzyme or dipeptidylpeptidase IV, while only two identified potentially novel drug targets for renal therapy. |
| 205 | 14630571 | The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are important in blood glucose regulation. |
| 206 | 14630571 | The concept of DPPIV inhibition as a treatment for type 2 diabetes was evaluated in a new large animal model of insulin-deficient diabetes and reduced beta-cell mass, the nicotinamide (NIA) (67 mg/kg) and streptozotocin (STZ) (125 mg/kg)-treated minipig, using the DPPIV inhibitor, valine pyrrolidide (VP) (50 mg/kg). |
| 207 | 14630571 | VP did not significantly affect levels of intact GLP-1 but increased levels of intact GIP (from 4543 +/- 1880 to 9208 +/- 3267 pM x min; P <.01), thus improving glucose tolerance (area under the curve [AUC] for glucose reduced from 1904 +/- 480 to 1582 +/- 353 mM x min; P =.05). |
| 208 | 14630571 | GIP seems to contribute to the antihyperglycemic effect of VP in this model; however, additional mechanisms for the effect of DPPIV inhibition cannot be excluded. |
| 209 | 14630571 | The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are important in blood glucose regulation. |
| 210 | 14630571 | The concept of DPPIV inhibition as a treatment for type 2 diabetes was evaluated in a new large animal model of insulin-deficient diabetes and reduced beta-cell mass, the nicotinamide (NIA) (67 mg/kg) and streptozotocin (STZ) (125 mg/kg)-treated minipig, using the DPPIV inhibitor, valine pyrrolidide (VP) (50 mg/kg). |
| 211 | 14630571 | VP did not significantly affect levels of intact GLP-1 but increased levels of intact GIP (from 4543 +/- 1880 to 9208 +/- 3267 pM x min; P <.01), thus improving glucose tolerance (area under the curve [AUC] for glucose reduced from 1904 +/- 480 to 1582 +/- 353 mM x min; P =.05). |
| 212 | 14630571 | GIP seems to contribute to the antihyperglycemic effect of VP in this model; however, additional mechanisms for the effect of DPPIV inhibition cannot be excluded. |
| 213 | 14718659 | Dipeptidyl peptidase IV (DPPIV) is a member of the prolyl oligopeptidase family of serine proteases. |
| 214 | 14718659 | To understand better the molecular determinants that underlie enzyme catalysis and substrate specificity, we report the crystal structures of DPPIV in the free form and in complex with the first 10 residues of the physiological substrate, Neuropeptide Y (residues 1-10; tNPY). |
| 215 | 14718659 | Dipeptidyl peptidase IV (DPPIV) is a member of the prolyl oligopeptidase family of serine proteases. |
| 216 | 14718659 | To understand better the molecular determinants that underlie enzyme catalysis and substrate specificity, we report the crystal structures of DPPIV in the free form and in complex with the first 10 residues of the physiological substrate, Neuropeptide Y (residues 1-10; tNPY). |
| 217 | 14719796 | Metabolic stability, receptor binding, cAMP generation, insulin secretion and antihyperglycaemic activity of novel N-terminal Glu9-substituted analogues of glucagon-like peptide-1. |
| 218 | 14719796 | Chemical modifications or substitutions of GLP-1 at His7 or Ala8 improve resistance to DPP-IV action, but this often reduces potency. |
| 219 | 14719796 | In addition, (Pro9)GLP-1 showed significant ability to moderate the plasma glucose excursion and increase circulating insulin concentrations in severely insulin resistant obese diabetic (ob/ob) mice. |
| 220 | 14767880 | Lys9 for Glu9 substitution in glucagon-like peptide-1(7-36)amide confers dipeptidylpeptidase IV resistance with cellular and metabolic actions similar to those of established antagonists glucagon-like peptide-1(9-36)amide and exendin (9-39). |
| 221 | 14767880 | Its effects, mediated through the regulation of insulin, glucagon, and somatostatin, are glucose-dependent and contribute to the tight control of glucose levels. |
| 222 | 15013938 | Extensive research during the past three decades has identified two gut hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP, also known as gastric inhibitory polypeptide) that are important in postprandial glucose metabolism. |
| 223 | 15013938 | Since they are potent insulin secretagogues, GIP and GLP-1 have received considerable attention as potential diabetes therapeutics. |
| 224 | 15013938 | Both GLP-1 and GIP are rapidly inactivated in the circulation by the enzyme dipeptidyl peptidase IV (DPP-IV). |
| 225 | 15013938 | Two approaches have been taken to utilise the insulinotropic and glucose-lowering actions of GLP-1 as an antidiabetic agent: the development of DPP-IV-resistant analogues and the inhibition of DPP-IV. |
| 226 | 15013938 | This review focuses on the physiology of GLP-1 and GIP and the advances that have been made thus far in developing treatments based on these physiological incretins for Type 2 diabetes. |
| 227 | 15013938 | Extensive research during the past three decades has identified two gut hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP, also known as gastric inhibitory polypeptide) that are important in postprandial glucose metabolism. |
| 228 | 15013938 | Since they are potent insulin secretagogues, GIP and GLP-1 have received considerable attention as potential diabetes therapeutics. |
| 229 | 15013938 | Both GLP-1 and GIP are rapidly inactivated in the circulation by the enzyme dipeptidyl peptidase IV (DPP-IV). |
| 230 | 15013938 | Two approaches have been taken to utilise the insulinotropic and glucose-lowering actions of GLP-1 as an antidiabetic agent: the development of DPP-IV-resistant analogues and the inhibition of DPP-IV. |
| 231 | 15013938 | This review focuses on the physiology of GLP-1 and GIP and the advances that have been made thus far in developing treatments based on these physiological incretins for Type 2 diabetes. |
| 232 | 15032621 | In particular, we will present recent data from our laboratory that demonstrates the correlation between CD26, especially its DPP IV activity, and the key nuclear protein topoisomerase II alpha, an interaction that has important clinical implications. |
| 233 | 15032621 | In summary, we will examine the biology of the multifaceted CD26/DPP IV molecule, focusing particularly on its function in immune regulation and its potential role as a molecular target for novel treatment modalities for a number of disease states, ranging from autoimmune diseases, diabetes to malignancies. |
| 234 | 15032621 | In particular, we will present recent data from our laboratory that demonstrates the correlation between CD26, especially its DPP IV activity, and the key nuclear protein topoisomerase II alpha, an interaction that has important clinical implications. |
| 235 | 15032621 | In summary, we will examine the biology of the multifaceted CD26/DPP IV molecule, focusing particularly on its function in immune regulation and its potential role as a molecular target for novel treatment modalities for a number of disease states, ranging from autoimmune diseases, diabetes to malignancies. |
| 236 | 15039452 | An incretin hormone, glucagon-like peptide-1 (GLP-1), has been shown to lower plasma glucose via glucose-dependent insulin secretion and to reduce appetite. |
| 237 | 15039452 | We previously found that the biguanide metformin, an antidiabetic agent, causes a significant increase of plasma active GLP-1 level in the presence of dipeptidyl peptidase IV (DPPIV) inhibitor in normal rats. |
| 238 | 15039452 | In an oral glucose tolerance test on day 1, the coadministration caused a greater improvement of glucose tolerance and a prominent increase of plasma active GLP-1 without marked insulin secretion. |
| 239 | 15039452 | These results demonstrate that the combination therapy of metformin with DPPIV inhibitor leads to reduced food intake and body weight gain, most likely through the significant increase of plasma GLP-1 level. |
| 240 | 15039452 | An incretin hormone, glucagon-like peptide-1 (GLP-1), has been shown to lower plasma glucose via glucose-dependent insulin secretion and to reduce appetite. |
| 241 | 15039452 | We previously found that the biguanide metformin, an antidiabetic agent, causes a significant increase of plasma active GLP-1 level in the presence of dipeptidyl peptidase IV (DPPIV) inhibitor in normal rats. |
| 242 | 15039452 | In an oral glucose tolerance test on day 1, the coadministration caused a greater improvement of glucose tolerance and a prominent increase of plasma active GLP-1 without marked insulin secretion. |
| 243 | 15039452 | These results demonstrate that the combination therapy of metformin with DPPIV inhibitor leads to reduced food intake and body weight gain, most likely through the significant increase of plasma GLP-1 level. |
| 244 | 15111503 | Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are gut-derived incretins that potentiate glucose clearance following nutrient ingestion. |
| 245 | 15111503 | Elimination of incretin receptor action in GIPR(-/-) or GLP-1R(-/-) mice produces only modest impairment in glucose homeostasis, perhaps due to compensatory upregulation of the remaining incretin. |
| 246 | 15111503 | DIRKO mice exhibit normal body weight and fail to exhibit an improved glycemic response after exogenous administration of GIP or the GLP-1R agonist exendin-4. |
| 247 | 15111503 | Glycemic excursion was abnormally increased and levels of glucose-stimulated insulin secretion were decreased following oral but not intraperitoneal glucose challenge in DIRKO compared with GIPR(-/-) or GLP-1R(-/-) mice. |
| 248 | 15111503 | Although the dipeptidyl peptidase-IV (DPP-IV) inhibitors valine pyrrolidide (Val-Pyr) and SYR106124 lowered glucose and increased plasma insulin in wild-type and single incretin receptor knockout mice, the glucose-lowering actions of DPP-IV inhibitors were eliminated in DIRKO mice. |
| 249 | 15111503 | These findings demonstrate that glucose-stimulated insulin secretion is maintained despite complete absence of both incretin receptors, and they delineate a critical role for incretin receptors as essential downstream targets for the acute glucoregulatory actions of DPP-IV inhibitors. |
| 250 | 15111503 | Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are gut-derived incretins that potentiate glucose clearance following nutrient ingestion. |
| 251 | 15111503 | Elimination of incretin receptor action in GIPR(-/-) or GLP-1R(-/-) mice produces only modest impairment in glucose homeostasis, perhaps due to compensatory upregulation of the remaining incretin. |
| 252 | 15111503 | DIRKO mice exhibit normal body weight and fail to exhibit an improved glycemic response after exogenous administration of GIP or the GLP-1R agonist exendin-4. |
| 253 | 15111503 | Glycemic excursion was abnormally increased and levels of glucose-stimulated insulin secretion were decreased following oral but not intraperitoneal glucose challenge in DIRKO compared with GIPR(-/-) or GLP-1R(-/-) mice. |
| 254 | 15111503 | Although the dipeptidyl peptidase-IV (DPP-IV) inhibitors valine pyrrolidide (Val-Pyr) and SYR106124 lowered glucose and increased plasma insulin in wild-type and single incretin receptor knockout mice, the glucose-lowering actions of DPP-IV inhibitors were eliminated in DIRKO mice. |
| 255 | 15111503 | These findings demonstrate that glucose-stimulated insulin secretion is maintained despite complete absence of both incretin receptors, and they delineate a critical role for incretin receptors as essential downstream targets for the acute glucoregulatory actions of DPP-IV inhibitors. |
| 256 | 15115400 | The catalytic action of DPP-IV is the principle means of degradation of glucagon-like peptide-1, a key mediator of glucose-stimulated insulin secretion, and DPP-IV inhibition shows clinical benefit as a novel mechanism for treatment of type 2 diabetes. |
| 257 | 15126524 | Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. |
| 258 | 15126524 | The stimulation of insulin vs. inhibition of glucagon secretion in relation to the antidiabetic action of glucagon-like peptide-1 (GLP-1) is not established. |
| 259 | 15126524 | Here, the influence of a 4-wk increase in circulating GLP-1 by inhibition of dipeptidyl peptidase-4 (DPP-4) on 24-h glucose and insulin and glucagon responses to breakfast was studied in subjects with dietary controlled diabetes [age: 65 +/- 8 yr (SD), body mass index: 27.3 +/- 3.3 kg/m(2), fasting plasma glucose: 9.0 +/- 1.3 mmol/liter]. |
| 260 | 15126524 | Thus, improved metabolic control by DPP-4 inhibition in type 2 diabetes is seen in association with reduced glucagon levels and, despite the lower glycemia, unaltered insulin levels. |
| 261 | 15126524 | Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. |
| 262 | 15126524 | The stimulation of insulin vs. inhibition of glucagon secretion in relation to the antidiabetic action of glucagon-like peptide-1 (GLP-1) is not established. |
| 263 | 15126524 | Here, the influence of a 4-wk increase in circulating GLP-1 by inhibition of dipeptidyl peptidase-4 (DPP-4) on 24-h glucose and insulin and glucagon responses to breakfast was studied in subjects with dietary controlled diabetes [age: 65 +/- 8 yr (SD), body mass index: 27.3 +/- 3.3 kg/m(2), fasting plasma glucose: 9.0 +/- 1.3 mmol/liter]. |
| 264 | 15126524 | Thus, improved metabolic control by DPP-4 inhibition in type 2 diabetes is seen in association with reduced glucagon levels and, despite the lower glycemia, unaltered insulin levels. |
| 265 | 15126524 | Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. |
| 266 | 15126524 | The stimulation of insulin vs. inhibition of glucagon secretion in relation to the antidiabetic action of glucagon-like peptide-1 (GLP-1) is not established. |
| 267 | 15126524 | Here, the influence of a 4-wk increase in circulating GLP-1 by inhibition of dipeptidyl peptidase-4 (DPP-4) on 24-h glucose and insulin and glucagon responses to breakfast was studied in subjects with dietary controlled diabetes [age: 65 +/- 8 yr (SD), body mass index: 27.3 +/- 3.3 kg/m(2), fasting plasma glucose: 9.0 +/- 1.3 mmol/liter]. |
| 268 | 15126524 | Thus, improved metabolic control by DPP-4 inhibition in type 2 diabetes is seen in association with reduced glucagon levels and, despite the lower glycemia, unaltered insulin levels. |
| 269 | 15143860 | Agonists of glucagon-like-peptide 1 (GLP-1) and antagonists of dipeptidylpeptidase IV, which inactivates GLP-1, stimulate glucose-dependent insulin secretion, improve hyperglycemia and are already tested in clinical trials. |
| 270 | 15143860 | In addition to clinically approved thiazolidendiones, new agonists of the peroxisome proliferator activator receptor gamma (PPAR gamma) as well as combined PPAR alpha/gamma agonists are developed at present. |
| 271 | 15155141 | Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP-IV inhibitors. |
| 272 | 15155141 | Glucagon-like peptide-1 (GLP-1) is a peptide hormone from the gut that stimulates insulin secretion and protects beta-cells, inhibits glucagon secretion and gastric emptying, and reduces appetite and food intake. |
| 273 | 15155141 | Instead, resistant analogues of the hormone (or agonists of the GLP-1 receptor) are in development, along with DPP-IV inhibitors, which have been demonstrated to protect the endogenous hormone and enhance its activity. |
| 274 | 15155141 | Agonists include both albumin-bound analogues of GLP-1 and exendin-4, a lizard peptide. |
| 275 | 15155141 | Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP-IV inhibitors. |
| 276 | 15155141 | Glucagon-like peptide-1 (GLP-1) is a peptide hormone from the gut that stimulates insulin secretion and protects beta-cells, inhibits glucagon secretion and gastric emptying, and reduces appetite and food intake. |
| 277 | 15155141 | Instead, resistant analogues of the hormone (or agonists of the GLP-1 receptor) are in development, along with DPP-IV inhibitors, which have been demonstrated to protect the endogenous hormone and enhance its activity. |
| 278 | 15155141 | Agonists include both albumin-bound analogues of GLP-1 and exendin-4, a lizard peptide. |
| 279 | 15331525 | GLP-1 is highly susceptible to enzymatic degradation in vivo, and cleavage by dipeptidyl peptidase IV (DPP-IV) is probably the most relevant, since this occurs rapidly and generates a noninsulinotropic metabolite. |
| 280 | 15331525 | Such strategies include DPP-IV-resistant GLP-1 analogs and selective enzyme inhibitors to prevent in vivo degradation of the peptide. |
| 281 | 15470600 | The majority of the presentations a the conference were on three highly sought-after targets for type 2 diabetes mellitus, namely PTP1B, PPARs and DPP-IV, reflecting the current focus and trend in the industry. |
| 282 | 15495988 | Upon ingestion of food, the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are synthesised and secreted by specialised gut cells. |
| 283 | 15495988 | GLP-1 and GIP stimulate beta-cell proliferation and differentiation, whereas GLP-1 only inhibits gastric emptying and glucagon secretion, reduces food intake and improves insulin sensitivity. |
| 284 | 15495988 | However, the insulinotropic action of exogenous GLP-1, but not that of GIP, is preserved in these subjects. |
| 285 | 15495988 | After parenteral administration, GLP-1 has an extremely short duration of action because it is rapidly degraded by the ubiquitous enzyme dipeptidyl peptidase IV (DPPIV). |
| 286 | 15495988 | To prolong GLP-1 bioactivity, DPPIV-resistant GLP-1 analogues, DPPIV inhibitors and exenatide, a long-acting synthetic GLP-1 receptor agonist derived from the Gila monster hormone exendin-4, have been developed. |
| 287 | 15495988 | Upon ingestion of food, the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are synthesised and secreted by specialised gut cells. |
| 288 | 15495988 | GLP-1 and GIP stimulate beta-cell proliferation and differentiation, whereas GLP-1 only inhibits gastric emptying and glucagon secretion, reduces food intake and improves insulin sensitivity. |
| 289 | 15495988 | However, the insulinotropic action of exogenous GLP-1, but not that of GIP, is preserved in these subjects. |
| 290 | 15495988 | After parenteral administration, GLP-1 has an extremely short duration of action because it is rapidly degraded by the ubiquitous enzyme dipeptidyl peptidase IV (DPPIV). |
| 291 | 15495988 | To prolong GLP-1 bioactivity, DPPIV-resistant GLP-1 analogues, DPPIV inhibitors and exenatide, a long-acting synthetic GLP-1 receptor agonist derived from the Gila monster hormone exendin-4, have been developed. |
| 292 | 15519151 | Dipeptidyl peptidase IV (DPP-IV) inhibitors have attracted attention as potential drugs for use in the treatment of type 2 diabetes because they prevent degradation of glucagon-like peptide-1 (GLP-1) and extend its duration of action. |
| 293 | 15604213 | Inhibition of dipeptidyl peptidase-4 augments insulin secretion in response to exogenously administered glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, pituitary adenylate cyclase-activating polypeptide, and gastrin-releasing peptide in mice. |
| 294 | 15604213 | In this study, we explored whether DPP-4 inhibition by valine-pyrrolidide (val-pyr; 100 micromol/kg administered through gastric gavage at t = -30 min) affects the insulin and glucose responses to iv glucose (1 g/kg) together with GLP-1 (10 nmol/kg), glucose-dependent insulinotropic polypeptide (GIP; 10 nmol/kg), pituitary adenylate cyclase-activating polypeptide 38 (PACAP38; 1.3 nmol/kg), or gastrin-releasing peptide (GRP; 20 nmol/kg) given at t = 0 in anesthetized C57BL/6J mice. |
| 295 | 15604213 | It was found that the acute (1-5 min) insulin response to GLP-1 was augmented by val-pyr by 80% (4.2 +/- 0.4 vs. 7.6 +/- 0.8 nmol/liter), that to GIP by 40% (2.7 +/- 0.3 vs. 3.8 +/- 0.4 nmol/liter), that to PACAP38 by 75% (4.6 +/- 0.5 vs. 8.1 +/- 0.6 nmol/liter), and that to GRP by 25% (1.8 +/- 0.2 vs. 2.3 +/- 0.3 nmol/liter; all P < 0.05 or less). |
| 296 | 15604213 | This was associated with enhanced glucose elimination rate after GLP-1 [glucose elimination constant (K(G)) 2.1 +/- 0.2 vs. 3.1 +/- 0.3%/min] and PACAP38 (2.1 +/- 0.3 vs. 3.2 +/- 0.3%/min; both P < 0.01), but not after GIP or GRP. |
| 297 | 15604213 | The augmented insulin response to GRP by val-pyr was prevented by the GLP-1 receptor antagonist, exendin(3) (9-39), raising the possibility that GRP effects may occur secondary to stimulation of GLP-1 secretion. |
| 298 | 15604213 | We conclude that DPP-4 inhibition augments the insulin response not only to GLP-1 but also to GIP, PACAP38, and GRP. |
| 299 | 15604213 | Inhibition of dipeptidyl peptidase-4 augments insulin secretion in response to exogenously administered glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, pituitary adenylate cyclase-activating polypeptide, and gastrin-releasing peptide in mice. |
| 300 | 15604213 | In this study, we explored whether DPP-4 inhibition by valine-pyrrolidide (val-pyr; 100 micromol/kg administered through gastric gavage at t = -30 min) affects the insulin and glucose responses to iv glucose (1 g/kg) together with GLP-1 (10 nmol/kg), glucose-dependent insulinotropic polypeptide (GIP; 10 nmol/kg), pituitary adenylate cyclase-activating polypeptide 38 (PACAP38; 1.3 nmol/kg), or gastrin-releasing peptide (GRP; 20 nmol/kg) given at t = 0 in anesthetized C57BL/6J mice. |
| 301 | 15604213 | It was found that the acute (1-5 min) insulin response to GLP-1 was augmented by val-pyr by 80% (4.2 +/- 0.4 vs. 7.6 +/- 0.8 nmol/liter), that to GIP by 40% (2.7 +/- 0.3 vs. 3.8 +/- 0.4 nmol/liter), that to PACAP38 by 75% (4.6 +/- 0.5 vs. 8.1 +/- 0.6 nmol/liter), and that to GRP by 25% (1.8 +/- 0.2 vs. 2.3 +/- 0.3 nmol/liter; all P < 0.05 or less). |
| 302 | 15604213 | This was associated with enhanced glucose elimination rate after GLP-1 [glucose elimination constant (K(G)) 2.1 +/- 0.2 vs. 3.1 +/- 0.3%/min] and PACAP38 (2.1 +/- 0.3 vs. 3.2 +/- 0.3%/min; both P < 0.01), but not after GIP or GRP. |
| 303 | 15604213 | The augmented insulin response to GRP by val-pyr was prevented by the GLP-1 receptor antagonist, exendin(3) (9-39), raising the possibility that GRP effects may occur secondary to stimulation of GLP-1 secretion. |
| 304 | 15604213 | We conclude that DPP-4 inhibition augments the insulin response not only to GLP-1 but also to GIP, PACAP38, and GRP. |
| 305 | 15604213 | Inhibition of dipeptidyl peptidase-4 augments insulin secretion in response to exogenously administered glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, pituitary adenylate cyclase-activating polypeptide, and gastrin-releasing peptide in mice. |
| 306 | 15604213 | In this study, we explored whether DPP-4 inhibition by valine-pyrrolidide (val-pyr; 100 micromol/kg administered through gastric gavage at t = -30 min) affects the insulin and glucose responses to iv glucose (1 g/kg) together with GLP-1 (10 nmol/kg), glucose-dependent insulinotropic polypeptide (GIP; 10 nmol/kg), pituitary adenylate cyclase-activating polypeptide 38 (PACAP38; 1.3 nmol/kg), or gastrin-releasing peptide (GRP; 20 nmol/kg) given at t = 0 in anesthetized C57BL/6J mice. |
| 307 | 15604213 | It was found that the acute (1-5 min) insulin response to GLP-1 was augmented by val-pyr by 80% (4.2 +/- 0.4 vs. 7.6 +/- 0.8 nmol/liter), that to GIP by 40% (2.7 +/- 0.3 vs. 3.8 +/- 0.4 nmol/liter), that to PACAP38 by 75% (4.6 +/- 0.5 vs. 8.1 +/- 0.6 nmol/liter), and that to GRP by 25% (1.8 +/- 0.2 vs. 2.3 +/- 0.3 nmol/liter; all P < 0.05 or less). |
| 308 | 15604213 | This was associated with enhanced glucose elimination rate after GLP-1 [glucose elimination constant (K(G)) 2.1 +/- 0.2 vs. 3.1 +/- 0.3%/min] and PACAP38 (2.1 +/- 0.3 vs. 3.2 +/- 0.3%/min; both P < 0.01), but not after GIP or GRP. |
| 309 | 15604213 | The augmented insulin response to GRP by val-pyr was prevented by the GLP-1 receptor antagonist, exendin(3) (9-39), raising the possibility that GRP effects may occur secondary to stimulation of GLP-1 secretion. |
| 310 | 15604213 | We conclude that DPP-4 inhibition augments the insulin response not only to GLP-1 but also to GIP, PACAP38, and GRP. |
| 311 | 15655721 | GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes. |
| 312 | 15655721 | Glucagon-like peptide-1 (GLP-1) is an incretin hormone with antidiabetic action through its ability to stimulate insulin secretion, increase beta cell neogenesis, inhibit beta cell apoptosis, inhibit glucagon secretion, delay gastric emptying and induce satiety. |
| 313 | 15655721 | A problem is, however, that GLP-1 is rapidly inactivated by the dipeptidyl peptidase-4 (DPP-4) enzyme, which results in a short circulating half-life of the active form of GLP-1 (< 2 min). |
| 314 | 15655721 | One is to use GLP-1 receptor agonists that have a prolonged half-life due to reduced degradation by DPP-4. |
| 315 | 15655721 | Another strategy is to inhibit the enzyme DPP-4, which prolongs the half-life of endogenously released active GLP-1. |
| 316 | 15655721 | GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes. |
| 317 | 15655721 | Glucagon-like peptide-1 (GLP-1) is an incretin hormone with antidiabetic action through its ability to stimulate insulin secretion, increase beta cell neogenesis, inhibit beta cell apoptosis, inhibit glucagon secretion, delay gastric emptying and induce satiety. |
| 318 | 15655721 | A problem is, however, that GLP-1 is rapidly inactivated by the dipeptidyl peptidase-4 (DPP-4) enzyme, which results in a short circulating half-life of the active form of GLP-1 (< 2 min). |
| 319 | 15655721 | One is to use GLP-1 receptor agonists that have a prolonged half-life due to reduced degradation by DPP-4. |
| 320 | 15655721 | Another strategy is to inhibit the enzyme DPP-4, which prolongs the half-life of endogenously released active GLP-1. |
| 321 | 15655721 | GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes. |
| 322 | 15655721 | Glucagon-like peptide-1 (GLP-1) is an incretin hormone with antidiabetic action through its ability to stimulate insulin secretion, increase beta cell neogenesis, inhibit beta cell apoptosis, inhibit glucagon secretion, delay gastric emptying and induce satiety. |
| 323 | 15655721 | A problem is, however, that GLP-1 is rapidly inactivated by the dipeptidyl peptidase-4 (DPP-4) enzyme, which results in a short circulating half-life of the active form of GLP-1 (< 2 min). |
| 324 | 15655721 | One is to use GLP-1 receptor agonists that have a prolonged half-life due to reduced degradation by DPP-4. |
| 325 | 15655721 | Another strategy is to inhibit the enzyme DPP-4, which prolongs the half-life of endogenously released active GLP-1. |
| 326 | 15655721 | GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes. |
| 327 | 15655721 | Glucagon-like peptide-1 (GLP-1) is an incretin hormone with antidiabetic action through its ability to stimulate insulin secretion, increase beta cell neogenesis, inhibit beta cell apoptosis, inhibit glucagon secretion, delay gastric emptying and induce satiety. |
| 328 | 15655721 | A problem is, however, that GLP-1 is rapidly inactivated by the dipeptidyl peptidase-4 (DPP-4) enzyme, which results in a short circulating half-life of the active form of GLP-1 (< 2 min). |
| 329 | 15655721 | One is to use GLP-1 receptor agonists that have a prolonged half-life due to reduced degradation by DPP-4. |
| 330 | 15655721 | Another strategy is to inhibit the enzyme DPP-4, which prolongs the half-life of endogenously released active GLP-1. |
| 331 | 15664838 | To identify potent and selective chemical compounds against DPP8, we have synthesized a series of isoquinoline and isoindoline derivatives and have tested their inhibitory activity against DPP8, DPP-IV and DPP-II. |
| 332 | 15664838 | Isoindoline with a 1-(4,4'-difluor-benzhydryl)-piperazine group at the P2 site was observed to be a very potent DPP8 inhibitor, having an IC(50) value of 14nM with at least a 2500-fold selectivity over either DPP-IV or DPP-II. |
| 333 | 15664838 | To identify potent and selective chemical compounds against DPP8, we have synthesized a series of isoquinoline and isoindoline derivatives and have tested their inhibitory activity against DPP8, DPP-IV and DPP-II. |
| 334 | 15664838 | Isoindoline with a 1-(4,4'-difluor-benzhydryl)-piperazine group at the P2 site was observed to be a very potent DPP8 inhibitor, having an IC(50) value of 14nM with at least a 2500-fold selectivity over either DPP-IV or DPP-II. |
| 335 | 15709922 | Because incretin actions are rapidly terminated by N-terminal cleavage of these peptide hormones by the amino-peptidase dipeptidyl peptidase IV (DPP IV, CD26), the utility of DPP IV inhibitors for the treatment of Type 2 diabetes is also under investigation. |
| 336 | 15765627 | GLP-1 administration stimulates glucose-dependent insulin secretion, inhibits glucagon secretion, and lowers blood glucose in normal and diabetic rodents and in humans. |
| 337 | 15765627 | The rapid N-terminal inactivation of bioactive GLP-1 by dipeptidyl peptidase-IV (DPP-IV) limits the utility of the native peptide for the treatment of patients with diabetes mellitus, and has fostered the development of more potent and stable protease-resistant GLP-1 analogs which exhibit longer durations of action. |
| 338 | 15765627 | The importance of DPP-IV for glucose control is illustrated by the phenotype of rodents with genetic inactivation of DPP-IV which exhibit reduced glycemic excursion and increased levels of circulating GLP-1 in vivo. |
| 339 | 15765627 | Inhibitors of DPP-IV potentiate incretin action by preventing degradation of GLP-1 and glucose-dependent insulinotropic peptide, and lower blood glucose in normal rodents and in experimental models of diabetes mellitus. |
| 340 | 15765627 | GLP-1 administration stimulates glucose-dependent insulin secretion, inhibits glucagon secretion, and lowers blood glucose in normal and diabetic rodents and in humans. |
| 341 | 15765627 | The rapid N-terminal inactivation of bioactive GLP-1 by dipeptidyl peptidase-IV (DPP-IV) limits the utility of the native peptide for the treatment of patients with diabetes mellitus, and has fostered the development of more potent and stable protease-resistant GLP-1 analogs which exhibit longer durations of action. |
| 342 | 15765627 | The importance of DPP-IV for glucose control is illustrated by the phenotype of rodents with genetic inactivation of DPP-IV which exhibit reduced glycemic excursion and increased levels of circulating GLP-1 in vivo. |
| 343 | 15765627 | Inhibitors of DPP-IV potentiate incretin action by preventing degradation of GLP-1 and glucose-dependent insulinotropic peptide, and lower blood glucose in normal rodents and in experimental models of diabetes mellitus. |
| 344 | 15765627 | GLP-1 administration stimulates glucose-dependent insulin secretion, inhibits glucagon secretion, and lowers blood glucose in normal and diabetic rodents and in humans. |
| 345 | 15765627 | The rapid N-terminal inactivation of bioactive GLP-1 by dipeptidyl peptidase-IV (DPP-IV) limits the utility of the native peptide for the treatment of patients with diabetes mellitus, and has fostered the development of more potent and stable protease-resistant GLP-1 analogs which exhibit longer durations of action. |
| 346 | 15765627 | The importance of DPP-IV for glucose control is illustrated by the phenotype of rodents with genetic inactivation of DPP-IV which exhibit reduced glycemic excursion and increased levels of circulating GLP-1 in vivo. |
| 347 | 15765627 | Inhibitors of DPP-IV potentiate incretin action by preventing degradation of GLP-1 and glucose-dependent insulinotropic peptide, and lower blood glucose in normal rodents and in experimental models of diabetes mellitus. |
| 348 | 15769092 | Glucagon-like peptide-1-(7-36) (GLP-1) is a hormone derived from the proglucagon molecule, which is considered a highly desirable antidiabetic agent mainly due to its unique glucose-dependent stimulation of insulin secretion profiles. |
| 349 | 15769092 | The in vitro insulinotropic effect of PEG(2k)-Lys-GLP-1 showed comparable biological activity with native GLP-1 (P = 0.11) in stimulating insulin secretion in isolated rat pancreatic islet and was significantly more potent than the PEG(2k)-N(ter)-GLP-1 (P < 0.05) that showed a marked reduced potency. |
| 350 | 15769092 | Furthermore, PEG(2k)-Lys-GLP-1 was clearly resistant to purified DPP-IV in buffer with 50-fold increased half-life compared to unmodified GLP-1. |
| 351 | 15769092 | These preliminary results suggest a site specifically mono-PEGylated GLP-1 greatly improved the pharmacological profiles; thus, we anticipated that it could serve as potential candidate as an antidiabetic agent for the treatment of non-insulin-dependent diabetes patients. |
| 352 | 15770466 | Their development is based on the observation that DPP-IV rapidly inactivates the incretin hormone glucagon-like peptide-1 (GLP-1), which is released postprandially from the gut and increases insulin secretion. |
| 353 | 15770466 | DPP-IV inhibitors stabilise endogenous GLP-1 at physiological concentrations, and induce insulin secretion in a glucose-dependent manner; therefore, they do not demonstrate any hypoglycaemic effects. |
| 354 | 15770466 | In addition to their ability to protect GLP-1 against degradation, DPP-IV inhibitors also stabilise other incretins, including gastric inhibitory peptide and pituitary adenylate cyclase-activating peptide. |
| 355 | 15770466 | Their development is based on the observation that DPP-IV rapidly inactivates the incretin hormone glucagon-like peptide-1 (GLP-1), which is released postprandially from the gut and increases insulin secretion. |
| 356 | 15770466 | DPP-IV inhibitors stabilise endogenous GLP-1 at physiological concentrations, and induce insulin secretion in a glucose-dependent manner; therefore, they do not demonstrate any hypoglycaemic effects. |
| 357 | 15770466 | In addition to their ability to protect GLP-1 against degradation, DPP-IV inhibitors also stabilise other incretins, including gastric inhibitory peptide and pituitary adenylate cyclase-activating peptide. |
| 358 | 15770466 | Their development is based on the observation that DPP-IV rapidly inactivates the incretin hormone glucagon-like peptide-1 (GLP-1), which is released postprandially from the gut and increases insulin secretion. |
| 359 | 15770466 | DPP-IV inhibitors stabilise endogenous GLP-1 at physiological concentrations, and induce insulin secretion in a glucose-dependent manner; therefore, they do not demonstrate any hypoglycaemic effects. |
| 360 | 15770466 | In addition to their ability to protect GLP-1 against degradation, DPP-IV inhibitors also stabilise other incretins, including gastric inhibitory peptide and pituitary adenylate cyclase-activating peptide. |
| 361 | 15780432 | GIP and GLP-1 as incretin hormones: lessons from single and double incretin receptor knockout mice. |
| 362 | 15780432 | Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut-derived incretins secreted in response to nutrient ingestion. |
| 363 | 15780432 | In contrast, GLP-1, but not GIP, inhibits gastric emptying, glucagon secretion, and food intake. |
| 364 | 15780432 | Furthermore, human subjects with Type 2 diabetes exhibit relative resistance to the actions of GIP, but not GLP-1R agonists. |
| 365 | 15780432 | However, glucose-stimulated insulin secretion is significantly decreased following oral but not intraperitoneal glucose challenge in DIRKO mice and the glucose lowering actions of dipeptidyl peptidase-IV (DPP-IV) inhibitors are extinguished in DIRKO mice. |
| 366 | 15786905 | A problem in developing this novel therapy is that GLP-1 is rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4), which results in a short half-life of the hormone requiring continuous infusion. |
| 367 | 15786905 | One strategy is the use of DPP-4 resistant GLP-1 receptor agonists (exenatide and liraglutide) and another strategy is to inhibit DPP-4 activity (LAF237). |
| 368 | 15786905 | A problem in developing this novel therapy is that GLP-1 is rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4), which results in a short half-life of the hormone requiring continuous infusion. |
| 369 | 15786905 | One strategy is the use of DPP-4 resistant GLP-1 receptor agonists (exenatide and liraglutide) and another strategy is to inhibit DPP-4 activity (LAF237). |
| 370 | 15852457 | The multifaceted actions of GLP-1 include the following: (1) the stimulation of insulin secretion and of its gene expression, (2) the inhibition of glucagon secretion, (3) the inhibition of food intake, (4) the proliferation and differentiation of beta cells, and (5) the protection of beta-cells from apoptosis. |
| 371 | 15852457 | The therapeutic utility of the native GLP-1 molecule is limited by its rapid enzymatic degradation by a serine protease termed dipeptidyl peptidase-IV (DPP-IV). |
| 372 | 15896683 | Dipeptidyl peptidase (DPP-IV) inhibitors suppress the degradation of many peptides, including GLP-1, thereby extending their bioactivity. |
| 373 | 16027230 | The enzyme dipeptidyl peptidase-IV (DPP-4) inactivates the incretin hormone glucagon-like peptide-1 (GLP-1). |
| 374 | 16027230 | Because GLP-1 has therapeutic effects in patients with type 2 diabetes, but its potential is limited by a short half-life, DPP-4 inhibition is a promising approach to diabetes treatment. |
| 375 | 16027230 | This study examined acute (single dose) and chronic (once-a-day dosing for 21 days) effects of the DPP-4 inhibitor vildagliptin (0.03-10 mg/kg) on plasma DPP-4 activity, intact GLP-1, glucose, and insulin after an oral glucose load in insulin-resistant Zucker fatty rats and acute effects in mildly insulin-resistant high-fat-fed normal rats. |
| 376 | 16027230 | The enzyme dipeptidyl peptidase-IV (DPP-4) inactivates the incretin hormone glucagon-like peptide-1 (GLP-1). |
| 377 | 16027230 | Because GLP-1 has therapeutic effects in patients with type 2 diabetes, but its potential is limited by a short half-life, DPP-4 inhibition is a promising approach to diabetes treatment. |
| 378 | 16027230 | This study examined acute (single dose) and chronic (once-a-day dosing for 21 days) effects of the DPP-4 inhibitor vildagliptin (0.03-10 mg/kg) on plasma DPP-4 activity, intact GLP-1, glucose, and insulin after an oral glucose load in insulin-resistant Zucker fatty rats and acute effects in mildly insulin-resistant high-fat-fed normal rats. |
| 379 | 16027230 | The enzyme dipeptidyl peptidase-IV (DPP-4) inactivates the incretin hormone glucagon-like peptide-1 (GLP-1). |
| 380 | 16027230 | Because GLP-1 has therapeutic effects in patients with type 2 diabetes, but its potential is limited by a short half-life, DPP-4 inhibition is a promising approach to diabetes treatment. |
| 381 | 16027230 | This study examined acute (single dose) and chronic (once-a-day dosing for 21 days) effects of the DPP-4 inhibitor vildagliptin (0.03-10 mg/kg) on plasma DPP-4 activity, intact GLP-1, glucose, and insulin after an oral glucose load in insulin-resistant Zucker fatty rats and acute effects in mildly insulin-resistant high-fat-fed normal rats. |
| 382 | 16035301 | The metabolic effects of glucagon-like peptide-1 (GLP-1) appear very promising, and can be either reproduced by long-acting GLP-1 analogues, or enhanced by inhibitors of dipeptidylpeptidase-IV, an enzyme that destroys GLP-1. |
| 383 | 16046120 | Dipeptidyl peptidase IV (DPP4) is a multifunctional type II transmembrane serine peptidase which regulates various physiological processes, most notably plasma glucose homeostasis by cleaving peptide hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. |
| 384 | 16106524 | Dipeptidyl peptidase-IV (DPP-IV) is involved in the inactivation of glucagon-like peptide-1 (GLP-1), a potent insulinotropic peptide. |
| 385 | 16106524 | Thus, DPP-IV inhibition can be an effective approach to treat type 2 diabetes mellitus by potentiating insulin secretion. |
| 386 | 16106524 | Administration of KR-62436 to C57BL/6J mice either orally or subcutaneously resulted in the suppression of plasma DPP-IV activity, increase in intact GLP-1 and insulin levels in plasma. |
| 387 | 16106524 | Dipeptidyl peptidase-IV (DPP-IV) is involved in the inactivation of glucagon-like peptide-1 (GLP-1), a potent insulinotropic peptide. |
| 388 | 16106524 | Thus, DPP-IV inhibition can be an effective approach to treat type 2 diabetes mellitus by potentiating insulin secretion. |
| 389 | 16106524 | Administration of KR-62436 to C57BL/6J mice either orally or subcutaneously resulted in the suppression of plasma DPP-IV activity, increase in intact GLP-1 and insulin levels in plasma. |
| 390 | 16106524 | Dipeptidyl peptidase-IV (DPP-IV) is involved in the inactivation of glucagon-like peptide-1 (GLP-1), a potent insulinotropic peptide. |
| 391 | 16106524 | Thus, DPP-IV inhibition can be an effective approach to treat type 2 diabetes mellitus by potentiating insulin secretion. |
| 392 | 16106524 | Administration of KR-62436 to C57BL/6J mice either orally or subcutaneously resulted in the suppression of plasma DPP-IV activity, increase in intact GLP-1 and insulin levels in plasma. |
| 393 | 16142014 | Biological actions of the incretins GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes. |
| 394 | 16142014 | In humans, the incretin effect is mainly caused by two peptide hormones, glucose-dependent insulin releasing polypeptide GIP, and glucagon-like peptide-1 GLP-1. |
| 395 | 16142014 | GIP is secreted by K cells from the upper small intestine while GLP-1 is mainly produced in the enteroendocrine L cells located in the distal intestine. |
| 396 | 16142014 | GIP and GLP-1 are both rapidly degraded into inactive metabolites by the enzyme dipeptidyl-peptidase-IV (DPP-IV). |
| 397 | 16142014 | In addition to its effects on insulin secretion, GLP-1 exerts other significant actions, including stimulation of insulin biosynthesis, inhibition of glucagon secretion, inhibition of gastric emptying and acid secretion, reduction of food intake, and trophic effects on the pancreas. |
| 398 | 16142014 | A number of pharmacological strategies have been developed to provide continuous delivery of GLP-1 and to prevent degradation of GLP-1, including continuous administration of GLP-1, DPP-IV inhibitors and DPP-IV resistant GLP-1 analogues. |
| 399 | 16142014 | Biological actions of the incretins GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes. |
| 400 | 16142014 | In humans, the incretin effect is mainly caused by two peptide hormones, glucose-dependent insulin releasing polypeptide GIP, and glucagon-like peptide-1 GLP-1. |
| 401 | 16142014 | GIP is secreted by K cells from the upper small intestine while GLP-1 is mainly produced in the enteroendocrine L cells located in the distal intestine. |
| 402 | 16142014 | GIP and GLP-1 are both rapidly degraded into inactive metabolites by the enzyme dipeptidyl-peptidase-IV (DPP-IV). |
| 403 | 16142014 | In addition to its effects on insulin secretion, GLP-1 exerts other significant actions, including stimulation of insulin biosynthesis, inhibition of glucagon secretion, inhibition of gastric emptying and acid secretion, reduction of food intake, and trophic effects on the pancreas. |
| 404 | 16142014 | A number of pharmacological strategies have been developed to provide continuous delivery of GLP-1 and to prevent degradation of GLP-1, including continuous administration of GLP-1, DPP-IV inhibitors and DPP-IV resistant GLP-1 analogues. |
| 405 | 16186403 | DPP-IV is a member of a family of serine peptidases that includes quiescent cell proline dipeptidase (QPP), DPP8, and DPP9; DPP-IV is a key regulator of incretin hormones, but the functions of other family members are unknown. |
| 406 | 16186403 | To determine the importance of selective DPP-IV inhibition for the treatment of diabetes, we tested selective inhibitors of DPP-IV, DPP8/DPP9, or QPP in 2-week rat toxicity studies and in acute dog tolerability studies. |
| 407 | 16186403 | The QPP inhibitor produced reticulocytopenia in rats only, and no toxicities were noted in either species for the selective DPP-IV inhibitor. |
| 408 | 16186403 | The DPP8/9 inhibitor was also shown to attenuate T-cell activation in human in vitro models; a selective DPP-IV inhibitor was inactive in these assays. |
| 409 | 16186403 | Moreover, we found DPP-IV inhibitors that were previously reported to be active in models of immune function to be more potent inhibitors of DPP8/9. |
| 410 | 16186403 | DPP-IV is a member of a family of serine peptidases that includes quiescent cell proline dipeptidase (QPP), DPP8, and DPP9; DPP-IV is a key regulator of incretin hormones, but the functions of other family members are unknown. |
| 411 | 16186403 | To determine the importance of selective DPP-IV inhibition for the treatment of diabetes, we tested selective inhibitors of DPP-IV, DPP8/DPP9, or QPP in 2-week rat toxicity studies and in acute dog tolerability studies. |
| 412 | 16186403 | The QPP inhibitor produced reticulocytopenia in rats only, and no toxicities were noted in either species for the selective DPP-IV inhibitor. |
| 413 | 16186403 | The DPP8/9 inhibitor was also shown to attenuate T-cell activation in human in vitro models; a selective DPP-IV inhibitor was inactive in these assays. |
| 414 | 16186403 | Moreover, we found DPP-IV inhibitors that were previously reported to be active in models of immune function to be more potent inhibitors of DPP8/9. |
| 415 | 16186403 | DPP-IV is a member of a family of serine peptidases that includes quiescent cell proline dipeptidase (QPP), DPP8, and DPP9; DPP-IV is a key regulator of incretin hormones, but the functions of other family members are unknown. |
| 416 | 16186403 | To determine the importance of selective DPP-IV inhibition for the treatment of diabetes, we tested selective inhibitors of DPP-IV, DPP8/DPP9, or QPP in 2-week rat toxicity studies and in acute dog tolerability studies. |
| 417 | 16186403 | The QPP inhibitor produced reticulocytopenia in rats only, and no toxicities were noted in either species for the selective DPP-IV inhibitor. |
| 418 | 16186403 | The DPP8/9 inhibitor was also shown to attenuate T-cell activation in human in vitro models; a selective DPP-IV inhibitor was inactive in these assays. |
| 419 | 16186403 | Moreover, we found DPP-IV inhibitors that were previously reported to be active in models of immune function to be more potent inhibitors of DPP8/9. |
| 420 | 16186403 | DPP-IV is a member of a family of serine peptidases that includes quiescent cell proline dipeptidase (QPP), DPP8, and DPP9; DPP-IV is a key regulator of incretin hormones, but the functions of other family members are unknown. |
| 421 | 16186403 | To determine the importance of selective DPP-IV inhibition for the treatment of diabetes, we tested selective inhibitors of DPP-IV, DPP8/DPP9, or QPP in 2-week rat toxicity studies and in acute dog tolerability studies. |
| 422 | 16186403 | The QPP inhibitor produced reticulocytopenia in rats only, and no toxicities were noted in either species for the selective DPP-IV inhibitor. |
| 423 | 16186403 | The DPP8/9 inhibitor was also shown to attenuate T-cell activation in human in vitro models; a selective DPP-IV inhibitor was inactive in these assays. |
| 424 | 16186403 | Moreover, we found DPP-IV inhibitors that were previously reported to be active in models of immune function to be more potent inhibitors of DPP8/9. |
| 425 | 16186403 | DPP-IV is a member of a family of serine peptidases that includes quiescent cell proline dipeptidase (QPP), DPP8, and DPP9; DPP-IV is a key regulator of incretin hormones, but the functions of other family members are unknown. |
| 426 | 16186403 | To determine the importance of selective DPP-IV inhibition for the treatment of diabetes, we tested selective inhibitors of DPP-IV, DPP8/DPP9, or QPP in 2-week rat toxicity studies and in acute dog tolerability studies. |
| 427 | 16186403 | The QPP inhibitor produced reticulocytopenia in rats only, and no toxicities were noted in either species for the selective DPP-IV inhibitor. |
| 428 | 16186403 | The DPP8/9 inhibitor was also shown to attenuate T-cell activation in human in vitro models; a selective DPP-IV inhibitor was inactive in these assays. |
| 429 | 16186403 | Moreover, we found DPP-IV inhibitors that were previously reported to be active in models of immune function to be more potent inhibitors of DPP8/9. |
| 430 | 16228047 | The GLP-1 derivatives have the advantage of decreasing body weight while the DPP-IV inhibitors can be administered orally up to once daily. |
| 431 | 16277173 | Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone, mainly secreted after meals, which enhances glucose-induced insulin secretion and induces satiety. |
| 432 | 16277173 | The reduction of post-prandial circulating active GLP-1 in Type 2 diabetic subjects, as a consequence of chronic hyperglycemia, could contribute to the reduction of early post-prandial insulin secretion; in fact, the administration of GLP-1 receptor antagonists to healthy volunteers elicits both an impairment of meal-induced insulin secretion and an increase of post-prandial glycemia similar to that observed in Type 2 diabetes. |
| 433 | 16277173 | GLP-1 is rapidly inactivated by dipeptidyl peptidase IV (DPP-IV), an enzyme produced by endothelial cells in different districts and that circulates in plasma. |
| 434 | 16277173 | There are now several compounds in various stages of pre-clinical or clinical development for the treatment of Type 2 diabetes that utilize the GLP-1 signaling pathway; these include GLP-1 receptor agonists with extended half-lives, and inhibitors of DPP-IV that increase circulating levels of endogenous, intact and bioactive GLP-1. |
| 435 | 16277173 | Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone, mainly secreted after meals, which enhances glucose-induced insulin secretion and induces satiety. |
| 436 | 16277173 | The reduction of post-prandial circulating active GLP-1 in Type 2 diabetic subjects, as a consequence of chronic hyperglycemia, could contribute to the reduction of early post-prandial insulin secretion; in fact, the administration of GLP-1 receptor antagonists to healthy volunteers elicits both an impairment of meal-induced insulin secretion and an increase of post-prandial glycemia similar to that observed in Type 2 diabetes. |
| 437 | 16277173 | GLP-1 is rapidly inactivated by dipeptidyl peptidase IV (DPP-IV), an enzyme produced by endothelial cells in different districts and that circulates in plasma. |
| 438 | 16277173 | There are now several compounds in various stages of pre-clinical or clinical development for the treatment of Type 2 diabetes that utilize the GLP-1 signaling pathway; these include GLP-1 receptor agonists with extended half-lives, and inhibitors of DPP-IV that increase circulating levels of endogenous, intact and bioactive GLP-1. |
| 439 | 16297991 | Identification of target genes of the transcription factor HNF1beta and HNF1alpha in a human embryonic kidney cell line. |
| 440 | 16297991 | By an identical approach, we identified that the related transcription factor HNF1alpha (TCF1) affects only nine genes in HEK293 cells and thus is a less efficient factor in these kidney cells. |
| 441 | 16297991 | The HNF1beta target genes dipeptidyl peptidase 4 (DPP4), angiotensin converting enzyme 2 (ACE2) and osteopontin (SPP1) are most likely direct target genes, as they contain functional HNF1 binding sites in their promoter region. |
| 442 | 16380482 | The SDF-1 receptor, CXCR4, is expressed in developing blood vessels as well as on CD34+ EPCs. |
| 443 | 16380482 | We describe that picomolar and nanomolar concentrations of SDF-1 differentially influence neovascularization, inducing CD34+ cell migration and EPC tube formation. |
| 444 | 16380482 | CD34+ cells isolated from diabetic patients demonstrate a marked defect in migration to SDF-1. |
| 445 | 16380482 | This defect is associated, in some but not all patients, with a cell surface activity of CD26/dipeptidyl peptidase IV, an enzyme that inactivates SDF-1. |
| 446 | 16380482 | Diabetic CD34+ cells also do not migrate in response to vascular endothelial growth factor and are structurally rigid. |
| 447 | 16385384 | The metabolite generated by dipeptidyl-peptidase 4 metabolism of glucagon-like peptide-1 has no influence on plasma glucose levels in patients with type 2 diabetes. |
| 448 | 16406202 | Pituitary adenylate cyclase-activating peptide (PACAP): assessment of dipeptidyl peptidase IV degradation, insulin-releasing activity and antidiabetic potential. |
| 449 | 16406202 | Pituitary adenylate cyclase-activating peptide (PACAP) is a member of the glucagon family of peptides. |
| 450 | 16406202 | Like other members, most notably glucagon-like peptide-1 (GLP-1), PACAP is rapidly degraded by dipeptidylpeptidase IV (DPP IV). |
| 451 | 16406202 | In contrast to 1.4-1.8-fold concentration-dependent stimulation of insulin secretion by PACAP(1-27), these peptide fragments lacked insulinotropic activity. |
| 452 | 16406202 | While PACAP(1-27) and PACAP(1-38) generated significant insulin responses when given alone or together with glucose in ob/ob and normal mice, they also elevated plasma glucose. |
| 453 | 16406202 | In conclusion, PACAP is inactivated by DPP IV and despite insulin-releasing effects, its actions on glucagon secretion and glucose homeostasis do not make it a good therapeutic tool for the treatment of type 2 diabetes. |
| 454 | 16409149 | Similarly, glucose-dependent insulinotropic polypeptide (GIP) receptor activation stimulates insulin secretion, enhances beta-cell proliferation, and reduces apoptosis. |
| 455 | 16409149 | Moreover, potentiation of the endogenous postprandial levels of GLP-1 and GIP via inhibition of dipeptidyl peptidase-IV (DPP-IV) also expands beta-cell mass via related mechanisms. |
| 456 | 16409149 | Complementary approaches to regeneration of beta-cell mass involve combinations of factors, exemplified by epidermal growth factor and gastrin, which promote islet neogenesis and ameliorate diabetes in rodent studies. |
| 457 | 16416146 | Gastric inhibitory polypeptide (GIP) was initially thought to regulate gastric acid secretion, whereas glucagon-like peptide-1 (GLP-1) was discovered as a result of a systematic search for intestinal insulinotropic products of proglucagon gene expression. |
| 458 | 16416146 | The incretin effect is markedly impaired or absent in patients with type 2 diabetes because of decreased secretion of GLP-1 and a loss of the insulinotropic effects of GIP. |
| 459 | 16416146 | Metabolic control can be restored or greatly improved by administration of exogenous GLP-1, but this peptide is almost immediately degraded by dipeptidyl peptidase IV (DPP-IV), and therefore has little clinical value. |
| 460 | 16416146 | DPP-IV-resistant analogues (incretin mimetics) have been identified or developed, and inhibitors of DPP-IV have also proved effective in protecting endogenous GLP-1 (and GIP) from degradation. |
| 461 | 16416146 | Gastric inhibitory polypeptide (GIP) was initially thought to regulate gastric acid secretion, whereas glucagon-like peptide-1 (GLP-1) was discovered as a result of a systematic search for intestinal insulinotropic products of proglucagon gene expression. |
| 462 | 16416146 | The incretin effect is markedly impaired or absent in patients with type 2 diabetes because of decreased secretion of GLP-1 and a loss of the insulinotropic effects of GIP. |
| 463 | 16416146 | Metabolic control can be restored or greatly improved by administration of exogenous GLP-1, but this peptide is almost immediately degraded by dipeptidyl peptidase IV (DPP-IV), and therefore has little clinical value. |
| 464 | 16416146 | DPP-IV-resistant analogues (incretin mimetics) have been identified or developed, and inhibitors of DPP-IV have also proved effective in protecting endogenous GLP-1 (and GIP) from degradation. |
| 465 | 16488579 | GLP-1 glucoregulatory actions include glucose-dependent enhancement of insulin secretion, inhibition of glucagon secretion, slowing of gastric emptying and reduction of food intake. |
| 466 | 16488579 | GLP-1 is rapidly inactivated by amino peptidase, dipeptidyl peptidase IV (DPP-IV) and the utility of DPP-IV inhibitors are also under investigation. |
| 467 | 16488579 | There is a recent upsurge in the development of GLP-1 mimetics and DPP-IV inhibitors as potential therapy for type 2 diabetes. |
| 468 | 16488579 | The present review summarizes the concepts of GLP-1 based therapy for type 2 diabetes and the current preclinical and clinical development in GLP-1 mimetics and DPP-IV inhibitors. |
| 469 | 16488579 | GLP-1 glucoregulatory actions include glucose-dependent enhancement of insulin secretion, inhibition of glucagon secretion, slowing of gastric emptying and reduction of food intake. |
| 470 | 16488579 | GLP-1 is rapidly inactivated by amino peptidase, dipeptidyl peptidase IV (DPP-IV) and the utility of DPP-IV inhibitors are also under investigation. |
| 471 | 16488579 | There is a recent upsurge in the development of GLP-1 mimetics and DPP-IV inhibitors as potential therapy for type 2 diabetes. |
| 472 | 16488579 | The present review summarizes the concepts of GLP-1 based therapy for type 2 diabetes and the current preclinical and clinical development in GLP-1 mimetics and DPP-IV inhibitors. |
| 473 | 16488579 | GLP-1 glucoregulatory actions include glucose-dependent enhancement of insulin secretion, inhibition of glucagon secretion, slowing of gastric emptying and reduction of food intake. |
| 474 | 16488579 | GLP-1 is rapidly inactivated by amino peptidase, dipeptidyl peptidase IV (DPP-IV) and the utility of DPP-IV inhibitors are also under investigation. |
| 475 | 16488579 | There is a recent upsurge in the development of GLP-1 mimetics and DPP-IV inhibitors as potential therapy for type 2 diabetes. |
| 476 | 16488579 | The present review summarizes the concepts of GLP-1 based therapy for type 2 diabetes and the current preclinical and clinical development in GLP-1 mimetics and DPP-IV inhibitors. |
| 477 | 16505481 | Design of a long acting peptide functioning as both a glucagon-like peptide-1 receptor agonist and a glucagon receptor antagonist. |
| 478 | 16505481 | GLP-1 induces glucose-dependent insulin secretion in the pancreas, whereas glucagon stimulates gluconeogenesis and glycogenolysis in the liver. |
| 479 | 16505481 | The presence of glucagon sequence at the N terminus removed the dipeptidylpeptidase IV cleavage site and increased plasma stability compared with GLP-1. |
| 480 | 16505481 | Targeted mutations were incorporated into the optimal dual-receptor binding peptide to identify a peptide with the highly novel property of functioning as both a GLP-1 receptor agonist and a glucagon receptor antagonist. |
| 481 | 16517403 | Gut peptides, exemplified by glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted in a nutrient-dependent manner and stimulate glucose-dependent insulin secretion. |
| 482 | 16517403 | Both GIP and GLP-1 also promote beta cell proliferation and inhibit apoptosis, leading to expansion of beta cell mass. |
| 483 | 16517403 | GLP-1, but not GIP, controls glycemia via additional actions on glucose sensors, inhibition of gastric emptying, food intake and glucagon secretion. |
| 484 | 16517403 | Furthermore, GLP-1, unlike GIP, potently stimulates insulin secretion and reduces blood glucose in human subjects with type 2 diabetes. |
| 485 | 16517403 | This article summarizes current concepts of incretin action and highlights the potential therapeutic utility of GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of type 2 diabetes. |
| 486 | 16548792 | Dipeptidyl peptidase-4 inhibitors act mainly by preventing the rapid degradation of glucagon-like peptide-1. |
| 487 | 16629719 | Glucagon-like peptide-1 (GLP-1) or agents that bind to its receptor (exenatide, Byetta) or agents that inhibit its destruction [dipeptidyl peptidase-IV (DPP-IV) inhibitors, Vildagliptin] improve insulin secretion, delay gastric emptying, and suppress glucagon secretion while decreasing food intake without increasing hypoglycemia. |
| 488 | 16731832 | Here, we investigated the effects of a potent and selective DPP-4 inhibitor, an analog of sitagliptin (des-fluoro-sitagliptin), on glycemic control and pancreatic beta-cell mass and function in a mouse model with defects in insulin sensitivity and secretion, namely high-fat diet (HFD) streptozotocin (STZ)-induced diabetic mice. |
| 489 | 16768443 | DPP-IV inactivates the glucagon-like peptide (GLP-1) and several other naturally produced bioactive peptides that contain preferentially a proline or alanine residue in the second amino acid sequence position by cleaving the N-terminal dipeptide. |
| 490 | 16781669 | Mutant HNF-1alpha and mutant HNF-1beta identified in MODY3 and MODY5 downregulate DPP-IV gene expression in Caco-2 cells. |
| 491 | 16781669 | Hepatocyte nuclear factors (HNF)-1alpha and HNF-1beta, known as the causal genes of MODY3 and MODY5, respectively, have been reported to be involved in regulation of DPP-IV gene expression. |
| 492 | 16781669 | But, it is not completely clear (i) that they play roles in regulation of DPP-IV gene expression, and (ii) whether DPP-IV gene activity is changed by mutant HNF-1alpha and mutant HNF-1beta in MODY3 and MODY5. |
| 493 | 16781669 | To explore these questions, we investigated transactivation effects of wild HNF-1alpha and 13 mutant HNF-1alpha, as well as wild HNF-1beta and 2 mutant HNF-1beta, on DPP-IV promoter luciferase gene in Caco-2 cells by means of a transient experiment. |
| 494 | 16781669 | Both wild HNF-1alpha and wild HNF-1beta significantly transactivated DPP-IV promoter, but mutant HNF-1alpha and mutant HNF-1beta exhibited low transactivation activity. |
| 495 | 16781669 | Moreover, to study whether mutant HNF-1alpha and mutant HNF-1beta change endogenous DPP-IV enzyme activity, we produced four stable cell lines from Caco-2 cells, in which wild HNF-1alpha or wild HNF-1beta, or else respective dominant-negative mutant HNF-1alphaT539fsdelC or dominant-negative mutant HNF-1betaR177X, was stably expressed. |
| 496 | 16781669 | We found that DPP-IV gene expression and enzyme activity were significantly increased in wild HNF-1alpha cells and wild HNF-1beta cells, whereas they decreased in HNF-1alphaT539fsdelC cells and HNF-1betaR177X cells, compared with DPP-IV gene expression and enzyme activity in Caco-2 cells. |
| 497 | 16781669 | These results suggest that both wild HNF-1alpha and wild HNF-1beta have a stimulatory effect on DPP-IV gene expression, but that mutant HNF-1alpha and mutant HNF-1beta attenuate the stimulatory effect. |
| 498 | 16781669 | Mutant HNF-1alpha and mutant HNF-1beta identified in MODY3 and MODY5 downregulate DPP-IV gene expression in Caco-2 cells. |
| 499 | 16781669 | Hepatocyte nuclear factors (HNF)-1alpha and HNF-1beta, known as the causal genes of MODY3 and MODY5, respectively, have been reported to be involved in regulation of DPP-IV gene expression. |
| 500 | 16781669 | But, it is not completely clear (i) that they play roles in regulation of DPP-IV gene expression, and (ii) whether DPP-IV gene activity is changed by mutant HNF-1alpha and mutant HNF-1beta in MODY3 and MODY5. |
| 501 | 16781669 | To explore these questions, we investigated transactivation effects of wild HNF-1alpha and 13 mutant HNF-1alpha, as well as wild HNF-1beta and 2 mutant HNF-1beta, on DPP-IV promoter luciferase gene in Caco-2 cells by means of a transient experiment. |
| 502 | 16781669 | Both wild HNF-1alpha and wild HNF-1beta significantly transactivated DPP-IV promoter, but mutant HNF-1alpha and mutant HNF-1beta exhibited low transactivation activity. |
| 503 | 16781669 | Moreover, to study whether mutant HNF-1alpha and mutant HNF-1beta change endogenous DPP-IV enzyme activity, we produced four stable cell lines from Caco-2 cells, in which wild HNF-1alpha or wild HNF-1beta, or else respective dominant-negative mutant HNF-1alphaT539fsdelC or dominant-negative mutant HNF-1betaR177X, was stably expressed. |
| 504 | 16781669 | We found that DPP-IV gene expression and enzyme activity were significantly increased in wild HNF-1alpha cells and wild HNF-1beta cells, whereas they decreased in HNF-1alphaT539fsdelC cells and HNF-1betaR177X cells, compared with DPP-IV gene expression and enzyme activity in Caco-2 cells. |
| 505 | 16781669 | These results suggest that both wild HNF-1alpha and wild HNF-1beta have a stimulatory effect on DPP-IV gene expression, but that mutant HNF-1alpha and mutant HNF-1beta attenuate the stimulatory effect. |
| 506 | 16781669 | Mutant HNF-1alpha and mutant HNF-1beta identified in MODY3 and MODY5 downregulate DPP-IV gene expression in Caco-2 cells. |
| 507 | 16781669 | Hepatocyte nuclear factors (HNF)-1alpha and HNF-1beta, known as the causal genes of MODY3 and MODY5, respectively, have been reported to be involved in regulation of DPP-IV gene expression. |
| 508 | 16781669 | But, it is not completely clear (i) that they play roles in regulation of DPP-IV gene expression, and (ii) whether DPP-IV gene activity is changed by mutant HNF-1alpha and mutant HNF-1beta in MODY3 and MODY5. |
| 509 | 16781669 | To explore these questions, we investigated transactivation effects of wild HNF-1alpha and 13 mutant HNF-1alpha, as well as wild HNF-1beta and 2 mutant HNF-1beta, on DPP-IV promoter luciferase gene in Caco-2 cells by means of a transient experiment. |
| 510 | 16781669 | Both wild HNF-1alpha and wild HNF-1beta significantly transactivated DPP-IV promoter, but mutant HNF-1alpha and mutant HNF-1beta exhibited low transactivation activity. |
| 511 | 16781669 | Moreover, to study whether mutant HNF-1alpha and mutant HNF-1beta change endogenous DPP-IV enzyme activity, we produced four stable cell lines from Caco-2 cells, in which wild HNF-1alpha or wild HNF-1beta, or else respective dominant-negative mutant HNF-1alphaT539fsdelC or dominant-negative mutant HNF-1betaR177X, was stably expressed. |
| 512 | 16781669 | We found that DPP-IV gene expression and enzyme activity were significantly increased in wild HNF-1alpha cells and wild HNF-1beta cells, whereas they decreased in HNF-1alphaT539fsdelC cells and HNF-1betaR177X cells, compared with DPP-IV gene expression and enzyme activity in Caco-2 cells. |
| 513 | 16781669 | These results suggest that both wild HNF-1alpha and wild HNF-1beta have a stimulatory effect on DPP-IV gene expression, but that mutant HNF-1alpha and mutant HNF-1beta attenuate the stimulatory effect. |
| 514 | 16781669 | Mutant HNF-1alpha and mutant HNF-1beta identified in MODY3 and MODY5 downregulate DPP-IV gene expression in Caco-2 cells. |
| 515 | 16781669 | Hepatocyte nuclear factors (HNF)-1alpha and HNF-1beta, known as the causal genes of MODY3 and MODY5, respectively, have been reported to be involved in regulation of DPP-IV gene expression. |
| 516 | 16781669 | But, it is not completely clear (i) that they play roles in regulation of DPP-IV gene expression, and (ii) whether DPP-IV gene activity is changed by mutant HNF-1alpha and mutant HNF-1beta in MODY3 and MODY5. |
| 517 | 16781669 | To explore these questions, we investigated transactivation effects of wild HNF-1alpha and 13 mutant HNF-1alpha, as well as wild HNF-1beta and 2 mutant HNF-1beta, on DPP-IV promoter luciferase gene in Caco-2 cells by means of a transient experiment. |
| 518 | 16781669 | Both wild HNF-1alpha and wild HNF-1beta significantly transactivated DPP-IV promoter, but mutant HNF-1alpha and mutant HNF-1beta exhibited low transactivation activity. |
| 519 | 16781669 | Moreover, to study whether mutant HNF-1alpha and mutant HNF-1beta change endogenous DPP-IV enzyme activity, we produced four stable cell lines from Caco-2 cells, in which wild HNF-1alpha or wild HNF-1beta, or else respective dominant-negative mutant HNF-1alphaT539fsdelC or dominant-negative mutant HNF-1betaR177X, was stably expressed. |
| 520 | 16781669 | We found that DPP-IV gene expression and enzyme activity were significantly increased in wild HNF-1alpha cells and wild HNF-1beta cells, whereas they decreased in HNF-1alphaT539fsdelC cells and HNF-1betaR177X cells, compared with DPP-IV gene expression and enzyme activity in Caco-2 cells. |
| 521 | 16781669 | These results suggest that both wild HNF-1alpha and wild HNF-1beta have a stimulatory effect on DPP-IV gene expression, but that mutant HNF-1alpha and mutant HNF-1beta attenuate the stimulatory effect. |
| 522 | 16781669 | Mutant HNF-1alpha and mutant HNF-1beta identified in MODY3 and MODY5 downregulate DPP-IV gene expression in Caco-2 cells. |
| 523 | 16781669 | Hepatocyte nuclear factors (HNF)-1alpha and HNF-1beta, known as the causal genes of MODY3 and MODY5, respectively, have been reported to be involved in regulation of DPP-IV gene expression. |
| 524 | 16781669 | But, it is not completely clear (i) that they play roles in regulation of DPP-IV gene expression, and (ii) whether DPP-IV gene activity is changed by mutant HNF-1alpha and mutant HNF-1beta in MODY3 and MODY5. |
| 525 | 16781669 | To explore these questions, we investigated transactivation effects of wild HNF-1alpha and 13 mutant HNF-1alpha, as well as wild HNF-1beta and 2 mutant HNF-1beta, on DPP-IV promoter luciferase gene in Caco-2 cells by means of a transient experiment. |
| 526 | 16781669 | Both wild HNF-1alpha and wild HNF-1beta significantly transactivated DPP-IV promoter, but mutant HNF-1alpha and mutant HNF-1beta exhibited low transactivation activity. |
| 527 | 16781669 | Moreover, to study whether mutant HNF-1alpha and mutant HNF-1beta change endogenous DPP-IV enzyme activity, we produced four stable cell lines from Caco-2 cells, in which wild HNF-1alpha or wild HNF-1beta, or else respective dominant-negative mutant HNF-1alphaT539fsdelC or dominant-negative mutant HNF-1betaR177X, was stably expressed. |
| 528 | 16781669 | We found that DPP-IV gene expression and enzyme activity were significantly increased in wild HNF-1alpha cells and wild HNF-1beta cells, whereas they decreased in HNF-1alphaT539fsdelC cells and HNF-1betaR177X cells, compared with DPP-IV gene expression and enzyme activity in Caco-2 cells. |
| 529 | 16781669 | These results suggest that both wild HNF-1alpha and wild HNF-1beta have a stimulatory effect on DPP-IV gene expression, but that mutant HNF-1alpha and mutant HNF-1beta attenuate the stimulatory effect. |
| 530 | 16781669 | Mutant HNF-1alpha and mutant HNF-1beta identified in MODY3 and MODY5 downregulate DPP-IV gene expression in Caco-2 cells. |
| 531 | 16781669 | Hepatocyte nuclear factors (HNF)-1alpha and HNF-1beta, known as the causal genes of MODY3 and MODY5, respectively, have been reported to be involved in regulation of DPP-IV gene expression. |
| 532 | 16781669 | But, it is not completely clear (i) that they play roles in regulation of DPP-IV gene expression, and (ii) whether DPP-IV gene activity is changed by mutant HNF-1alpha and mutant HNF-1beta in MODY3 and MODY5. |
| 533 | 16781669 | To explore these questions, we investigated transactivation effects of wild HNF-1alpha and 13 mutant HNF-1alpha, as well as wild HNF-1beta and 2 mutant HNF-1beta, on DPP-IV promoter luciferase gene in Caco-2 cells by means of a transient experiment. |
| 534 | 16781669 | Both wild HNF-1alpha and wild HNF-1beta significantly transactivated DPP-IV promoter, but mutant HNF-1alpha and mutant HNF-1beta exhibited low transactivation activity. |
| 535 | 16781669 | Moreover, to study whether mutant HNF-1alpha and mutant HNF-1beta change endogenous DPP-IV enzyme activity, we produced four stable cell lines from Caco-2 cells, in which wild HNF-1alpha or wild HNF-1beta, or else respective dominant-negative mutant HNF-1alphaT539fsdelC or dominant-negative mutant HNF-1betaR177X, was stably expressed. |
| 536 | 16781669 | We found that DPP-IV gene expression and enzyme activity were significantly increased in wild HNF-1alpha cells and wild HNF-1beta cells, whereas they decreased in HNF-1alphaT539fsdelC cells and HNF-1betaR177X cells, compared with DPP-IV gene expression and enzyme activity in Caco-2 cells. |
| 537 | 16781669 | These results suggest that both wild HNF-1alpha and wild HNF-1beta have a stimulatory effect on DPP-IV gene expression, but that mutant HNF-1alpha and mutant HNF-1beta attenuate the stimulatory effect. |
| 538 | 16781669 | Mutant HNF-1alpha and mutant HNF-1beta identified in MODY3 and MODY5 downregulate DPP-IV gene expression in Caco-2 cells. |
| 539 | 16781669 | Hepatocyte nuclear factors (HNF)-1alpha and HNF-1beta, known as the causal genes of MODY3 and MODY5, respectively, have been reported to be involved in regulation of DPP-IV gene expression. |
| 540 | 16781669 | But, it is not completely clear (i) that they play roles in regulation of DPP-IV gene expression, and (ii) whether DPP-IV gene activity is changed by mutant HNF-1alpha and mutant HNF-1beta in MODY3 and MODY5. |
| 541 | 16781669 | To explore these questions, we investigated transactivation effects of wild HNF-1alpha and 13 mutant HNF-1alpha, as well as wild HNF-1beta and 2 mutant HNF-1beta, on DPP-IV promoter luciferase gene in Caco-2 cells by means of a transient experiment. |
| 542 | 16781669 | Both wild HNF-1alpha and wild HNF-1beta significantly transactivated DPP-IV promoter, but mutant HNF-1alpha and mutant HNF-1beta exhibited low transactivation activity. |
| 543 | 16781669 | Moreover, to study whether mutant HNF-1alpha and mutant HNF-1beta change endogenous DPP-IV enzyme activity, we produced four stable cell lines from Caco-2 cells, in which wild HNF-1alpha or wild HNF-1beta, or else respective dominant-negative mutant HNF-1alphaT539fsdelC or dominant-negative mutant HNF-1betaR177X, was stably expressed. |
| 544 | 16781669 | We found that DPP-IV gene expression and enzyme activity were significantly increased in wild HNF-1alpha cells and wild HNF-1beta cells, whereas they decreased in HNF-1alphaT539fsdelC cells and HNF-1betaR177X cells, compared with DPP-IV gene expression and enzyme activity in Caco-2 cells. |
| 545 | 16781669 | These results suggest that both wild HNF-1alpha and wild HNF-1beta have a stimulatory effect on DPP-IV gene expression, but that mutant HNF-1alpha and mutant HNF-1beta attenuate the stimulatory effect. |
| 546 | 16781669 | Mutant HNF-1alpha and mutant HNF-1beta identified in MODY3 and MODY5 downregulate DPP-IV gene expression in Caco-2 cells. |
| 547 | 16781669 | Hepatocyte nuclear factors (HNF)-1alpha and HNF-1beta, known as the causal genes of MODY3 and MODY5, respectively, have been reported to be involved in regulation of DPP-IV gene expression. |
| 548 | 16781669 | But, it is not completely clear (i) that they play roles in regulation of DPP-IV gene expression, and (ii) whether DPP-IV gene activity is changed by mutant HNF-1alpha and mutant HNF-1beta in MODY3 and MODY5. |
| 549 | 16781669 | To explore these questions, we investigated transactivation effects of wild HNF-1alpha and 13 mutant HNF-1alpha, as well as wild HNF-1beta and 2 mutant HNF-1beta, on DPP-IV promoter luciferase gene in Caco-2 cells by means of a transient experiment. |
| 550 | 16781669 | Both wild HNF-1alpha and wild HNF-1beta significantly transactivated DPP-IV promoter, but mutant HNF-1alpha and mutant HNF-1beta exhibited low transactivation activity. |
| 551 | 16781669 | Moreover, to study whether mutant HNF-1alpha and mutant HNF-1beta change endogenous DPP-IV enzyme activity, we produced four stable cell lines from Caco-2 cells, in which wild HNF-1alpha or wild HNF-1beta, or else respective dominant-negative mutant HNF-1alphaT539fsdelC or dominant-negative mutant HNF-1betaR177X, was stably expressed. |
| 552 | 16781669 | We found that DPP-IV gene expression and enzyme activity were significantly increased in wild HNF-1alpha cells and wild HNF-1beta cells, whereas they decreased in HNF-1alphaT539fsdelC cells and HNF-1betaR177X cells, compared with DPP-IV gene expression and enzyme activity in Caco-2 cells. |
| 553 | 16781669 | These results suggest that both wild HNF-1alpha and wild HNF-1beta have a stimulatory effect on DPP-IV gene expression, but that mutant HNF-1alpha and mutant HNF-1beta attenuate the stimulatory effect. |
| 554 | 16800760 | Novel therapies that leverage the so-called "incretin effect" of GLP-1 (including the incretin mimetics and dipeptidyl peptidase-IV (DPP-IV) inhibitors) are being actively developed for the management of type 2 diabetes. |
| 555 | 16800760 | DPP-IV inhibitors enhance the concentration of endogenous GLP-1 by limiting proteolysis of native GLP-1. |
| 556 | 16800760 | Novel therapies that leverage the so-called "incretin effect" of GLP-1 (including the incretin mimetics and dipeptidyl peptidase-IV (DPP-IV) inhibitors) are being actively developed for the management of type 2 diabetes. |
| 557 | 16800760 | DPP-IV inhibitors enhance the concentration of endogenous GLP-1 by limiting proteolysis of native GLP-1. |
| 558 | 16835316 | Attractin, a dipeptidyl peptidase IV/CD26-like enzyme, is expressed on human peripheral blood monocytes and potentially influences monocyte function. |
| 559 | 16835316 | Moreover, this inhibitor significantly modulates the production of interleukin-1 (IL-1) receptor antagonist, IL-6, and transforming growth factor-beta1 in lipopolysaccharide-stimulated monocyte cultures. |
| 560 | 16855072 | Sitagliptin treatment led to approximately 90% inhibition of plasma DPP-4 activity, increased active glucagon-like peptide-1 (GLP-1) levels by 2.7-fold (P < .001), and decreased post-oral glucose tolerance test glucose excursion by 35% (P < .050) compared to placebo. |
| 561 | 16855072 | In nondiabetic obese subjects, treatment with sitagliptin 200 mg bid was generally well tolerated without associated hypoglycemia and led to maximal inhibition of plasma DPP-4 activity, increased active GLP-1, and reduced glycemic excursion. |
| 562 | 16855072 | Sitagliptin treatment led to approximately 90% inhibition of plasma DPP-4 activity, increased active glucagon-like peptide-1 (GLP-1) levels by 2.7-fold (P < .001), and decreased post-oral glucose tolerance test glucose excursion by 35% (P < .050) compared to placebo. |
| 563 | 16855072 | In nondiabetic obese subjects, treatment with sitagliptin 200 mg bid was generally well tolerated without associated hypoglycemia and led to maximal inhibition of plasma DPP-4 activity, increased active GLP-1, and reduced glycemic excursion. |
| 564 | 16946406 | The enzyme dipeptidyl peptidase-IV (DPP-IV) inactivates a variety of bioactive peptides, including glucagon-like peptide-1 (GLP-1) and growth hormone releasing hormone (GHRH). |
| 565 | 16946406 | Inhibiting DPP-IV in order to increase circulating GLP-1 is of interest as a treatment for Type II diabetes. |
| 566 | 16946406 | Inactivation of DPP-IV may also increase circulating GHRH, potentially enhancing growth in domestic animals. |
| 567 | 16946406 | To test the hypothesis that inhibition of DPP-IV activity will influence the growth hormone/ IGF-1 axis, growing pigs (Sus scrofa domesticus, 78 kg) were treated with a DPP-IV inhibitor (Compound 1, the 2,5-difluor-ophenyl analog of the triazolopiperazine MK0431, sitagliptin), and plasma concentrations of IGF-1 were monitored. |
| 568 | 16946406 | GHRH treatment increased the IGF-1 AUC (1210 +/- 160 ng/ml x hr, P = 0.049 vs. controls and P = 0.001 vs. |
| 569 | 16946406 | We conclude that inhibition of DPP-IV does not alter the circulating levels of IGF-1 in the growing pig. |
| 570 | 16946406 | The enzyme dipeptidyl peptidase-IV (DPP-IV) inactivates a variety of bioactive peptides, including glucagon-like peptide-1 (GLP-1) and growth hormone releasing hormone (GHRH). |
| 571 | 16946406 | Inhibiting DPP-IV in order to increase circulating GLP-1 is of interest as a treatment for Type II diabetes. |
| 572 | 16946406 | Inactivation of DPP-IV may also increase circulating GHRH, potentially enhancing growth in domestic animals. |
| 573 | 16946406 | To test the hypothesis that inhibition of DPP-IV activity will influence the growth hormone/ IGF-1 axis, growing pigs (Sus scrofa domesticus, 78 kg) were treated with a DPP-IV inhibitor (Compound 1, the 2,5-difluor-ophenyl analog of the triazolopiperazine MK0431, sitagliptin), and plasma concentrations of IGF-1 were monitored. |
| 574 | 16946406 | GHRH treatment increased the IGF-1 AUC (1210 +/- 160 ng/ml x hr, P = 0.049 vs. controls and P = 0.001 vs. |
| 575 | 16946406 | We conclude that inhibition of DPP-IV does not alter the circulating levels of IGF-1 in the growing pig. |
| 576 | 16946406 | The enzyme dipeptidyl peptidase-IV (DPP-IV) inactivates a variety of bioactive peptides, including glucagon-like peptide-1 (GLP-1) and growth hormone releasing hormone (GHRH). |
| 577 | 16946406 | Inhibiting DPP-IV in order to increase circulating GLP-1 is of interest as a treatment for Type II diabetes. |
| 578 | 16946406 | Inactivation of DPP-IV may also increase circulating GHRH, potentially enhancing growth in domestic animals. |
| 579 | 16946406 | To test the hypothesis that inhibition of DPP-IV activity will influence the growth hormone/ IGF-1 axis, growing pigs (Sus scrofa domesticus, 78 kg) were treated with a DPP-IV inhibitor (Compound 1, the 2,5-difluor-ophenyl analog of the triazolopiperazine MK0431, sitagliptin), and plasma concentrations of IGF-1 were monitored. |
| 580 | 16946406 | GHRH treatment increased the IGF-1 AUC (1210 +/- 160 ng/ml x hr, P = 0.049 vs. controls and P = 0.001 vs. |
| 581 | 16946406 | We conclude that inhibition of DPP-IV does not alter the circulating levels of IGF-1 in the growing pig. |
| 582 | 16946406 | The enzyme dipeptidyl peptidase-IV (DPP-IV) inactivates a variety of bioactive peptides, including glucagon-like peptide-1 (GLP-1) and growth hormone releasing hormone (GHRH). |
| 583 | 16946406 | Inhibiting DPP-IV in order to increase circulating GLP-1 is of interest as a treatment for Type II diabetes. |
| 584 | 16946406 | Inactivation of DPP-IV may also increase circulating GHRH, potentially enhancing growth in domestic animals. |
| 585 | 16946406 | To test the hypothesis that inhibition of DPP-IV activity will influence the growth hormone/ IGF-1 axis, growing pigs (Sus scrofa domesticus, 78 kg) were treated with a DPP-IV inhibitor (Compound 1, the 2,5-difluor-ophenyl analog of the triazolopiperazine MK0431, sitagliptin), and plasma concentrations of IGF-1 were monitored. |
| 586 | 16946406 | GHRH treatment increased the IGF-1 AUC (1210 +/- 160 ng/ml x hr, P = 0.049 vs. controls and P = 0.001 vs. |
| 587 | 16946406 | We conclude that inhibition of DPP-IV does not alter the circulating levels of IGF-1 in the growing pig. |
| 588 | 16946406 | The enzyme dipeptidyl peptidase-IV (DPP-IV) inactivates a variety of bioactive peptides, including glucagon-like peptide-1 (GLP-1) and growth hormone releasing hormone (GHRH). |
| 589 | 16946406 | Inhibiting DPP-IV in order to increase circulating GLP-1 is of interest as a treatment for Type II diabetes. |
| 590 | 16946406 | Inactivation of DPP-IV may also increase circulating GHRH, potentially enhancing growth in domestic animals. |
| 591 | 16946406 | To test the hypothesis that inhibition of DPP-IV activity will influence the growth hormone/ IGF-1 axis, growing pigs (Sus scrofa domesticus, 78 kg) were treated with a DPP-IV inhibitor (Compound 1, the 2,5-difluor-ophenyl analog of the triazolopiperazine MK0431, sitagliptin), and plasma concentrations of IGF-1 were monitored. |
| 592 | 16946406 | GHRH treatment increased the IGF-1 AUC (1210 +/- 160 ng/ml x hr, P = 0.049 vs. controls and P = 0.001 vs. |
| 593 | 16946406 | We conclude that inhibition of DPP-IV does not alter the circulating levels of IGF-1 in the growing pig. |
| 594 | 16980568 | The trifluoroacetate salt form of ER-319711, ER-319711-15, inhibited human DPP-IV with an IC(50) value of 0.089 microM, whereas its IC(50) values toward human DPP8 and DPP9 were >100 microM. |
| 595 | 16980568 | ER-319711-15 (1 mg/kg) reduced glucose excursion in an oral glucose tolerance test (OGTT) using Zucker fa/fa rats, with significant increases in plasma insulin and active glucagon-like peptide-1 levels. |
| 596 | 17034148 | Structure-activity studies of substitutions at the C5 position of the 2-cyanopyrrolidide warhead led to the discovery of potent inhibitors of DPP-IV that lack activity against DPP8 and DPP9. |
| 597 | 17034148 | Further modification led to an extremely potent (Ki(DPP)(-)(IV) = 1.0 nM) and selective (Ki(DPP8) > 30 microM; Ki(DPP9) > 30 microM) clinical candidate, ABT-279, that is orally available, efficacious, and remarkably safe in preclinical safety studies. |
| 598 | 17064063 | Dipeptidyl peptidase IV (DPP4) deactivates glucose-regulating hormones such as GLP-1 and GIP, thus, DPP4 inhibition has become a useful therapy for type 2 diabetes. |
| 599 | 17090794 | Dipeptidyl peptidase-IV (DPP-IV) inhibitors suppress the degradation of many peptides, including GLP-1, thereby extending their bioactivity. |
| 600 | 17090794 | Several GLP-1 analogues and DPP-IV inhibitors are in late-stage clinical testing and may soon become available for treating T2DM patients. |
| 601 | 17090794 | Dipeptidyl peptidase-IV (DPP-IV) inhibitors suppress the degradation of many peptides, including GLP-1, thereby extending their bioactivity. |
| 602 | 17090794 | Several GLP-1 analogues and DPP-IV inhibitors are in late-stage clinical testing and may soon become available for treating T2DM patients. |
| 603 | 17093132 | In this study, we have examined the effects of combining a novel, selective, and competitive dipeptidyl peptidase IV (DPP-IV) inhibitor, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate (E3024), with a representative of one of two types of insulin secretagogues, i.e., either glybenclamide (a sulfonylurea) or nateglinide (a rapid-onset/short-duration insulin secretagogue), on glucose and insulin levels in an oral glucose tolerance test (OGTT) using mice fed a high-fat diet. |
| 604 | 17098089 | The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. |
| 605 | 17098089 | Glucagon-like peptide 1 (GLP-1) is a gut-derived incretin hormone that stimulates insulin and suppresses glucagon secretion, inhibits gastric emptying, and reduces appetite and food intake. |
| 606 | 17098089 | Therapeutic approaches for enhancing incretin action include degradation-resistant GLP-1 receptor agonists (incretin mimetics), and inhibitors of dipeptidyl peptidase-4 (DPP-4) activity (incretin enhancers). |
| 607 | 17098089 | The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. |
| 608 | 17098089 | Glucagon-like peptide 1 (GLP-1) is a gut-derived incretin hormone that stimulates insulin and suppresses glucagon secretion, inhibits gastric emptying, and reduces appetite and food intake. |
| 609 | 17098089 | Therapeutic approaches for enhancing incretin action include degradation-resistant GLP-1 receptor agonists (incretin mimetics), and inhibitors of dipeptidyl peptidase-4 (DPP-4) activity (incretin enhancers). |
| 610 | 17100408 | It improves glycaemic control by inhibiting DPP-4 from inactivating the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, prolonging incretin activity in response to ingestion of nutrients. |
| 611 | 17149884 | VPAC2P-PEG is a VPAC2 receptor agonist peptide that acts as a glucose-dependent insulin secretagogue. |
| 612 | 17149884 | The acetylated peptide, Ac-VPAC2P-PEG, is a selective and potent VPAC2 agonist, resistant to DPPIV proteolysis, and exhibits substantially improved half-life and glucose disposal in rodents. |
| 613 | 17258675 | Drug treatment of 2 diabetes is intended to normalize glycosylated hemoglobin levels (HbA(1c)<6.5%) and thereby prevent the development of micro- and macrovascular complications. |
| 614 | 17258675 | GLP-1 (Glucagon-Like Peptide-1) analogs and DPP-IV (dipeptidyl-peptidase-IV) inhibitors are new drug classes currently under development. |
| 615 | 17263764 | Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone, released postprandially,which stimulates insulin secretion and insulin gene expression as well as pancreatic B-cell growth. |
| 616 | 17263764 | Together with glucose-dependent insulinotropic polypeptide (GIP), it is responsible for the incretin effect which is the augmentation of insulin secretion following oral administration of glucose. |
| 617 | 17263764 | Patients with Type 2 diabetes have greatly impaired or absent incretin-mediated insulin secretion which is mainly as a result of decreased secretion of GLP-1. |
| 618 | 17263764 | In addition to stimulating insulin secretion and promoting pancreatic B-cell mass, GLP-1 suppresses glucagon secretion,delays gastric emptying and inhibits food intake. |
| 619 | 17263764 | However, GLP-1 is metabolized extremely rapidly in the circulation by the enzyme dipeptidyl peptidase IV(DPP-IV). |
| 620 | 17267075 | Glucagon-like peptide-1 (GLP-1) stimulates insulin and inhibits glucagon secretion and therefore could potentially be used to treat diabetes type II. |
| 621 | 17267075 | This assay was functionally based using the GLP-1 receptor (GLP-1R) gene. |
| 622 | 17267075 | Although KS-12 was not as effective as GLP-1, it was significantly resistant to DPP-IV both in vitro and in vivo. |
| 623 | 17267075 | Thus, this study provides a novel way to screen DPP-IV resistant agonist peptides of GLP-1 from a PhD peptide library using the functional reporter gene HTS assay. |
| 624 | 17267075 | Glucagon-like peptide-1 (GLP-1) stimulates insulin and inhibits glucagon secretion and therefore could potentially be used to treat diabetes type II. |
| 625 | 17267075 | This assay was functionally based using the GLP-1 receptor (GLP-1R) gene. |
| 626 | 17267075 | Although KS-12 was not as effective as GLP-1, it was significantly resistant to DPP-IV both in vitro and in vivo. |
| 627 | 17267075 | Thus, this study provides a novel way to screen DPP-IV resistant agonist peptides of GLP-1 from a PhD peptide library using the functional reporter gene HTS assay. |
| 628 | 17287297 | Until now, only recombinant forms of DPP8 and DPP9 have been characterized. |
| 629 | 17287297 | All leukocyte types tested (lymphocytes, monocytes, Jurkat, and U937 cells) were shown to contain similar DPP8/9-specific activities, and DPPII- and DPPIV-specific activities varied considerably. |
| 630 | 17287297 | Subcellular fractionation localized the preponderance of DPP8/9 activity to the cytosol and DPPIV in the membrane fractions. |
| 631 | 17287297 | Until now, only recombinant forms of DPP8 and DPP9 have been characterized. |
| 632 | 17287297 | All leukocyte types tested (lymphocytes, monocytes, Jurkat, and U937 cells) were shown to contain similar DPP8/9-specific activities, and DPPII- and DPPIV-specific activities varied considerably. |
| 633 | 17287297 | Subcellular fractionation localized the preponderance of DPP8/9 activity to the cytosol and DPPIV in the membrane fractions. |
| 634 | 17300591 | DPP-IV inhibitors, therefore, increase circulating levels and prolong the biological activity of endogenous GLP-1, but whether this is sufficient to fully explain the substantial reduction in haemoglobin A(1c) (HbA(1c)) and associated metabolic profile remains open to further investigation. |
| 635 | 17300591 | DPP-IV inhibitors such as vildagliptin and sitagliptin have been shown to be highly effective antihyperglycaemic agents that augment insulin secretion and reduce glucagon secretion via glucose-dependent mechanisms. |
| 636 | 17300591 | DPP-IV inhibitors, therefore, increase circulating levels and prolong the biological activity of endogenous GLP-1, but whether this is sufficient to fully explain the substantial reduction in haemoglobin A(1c) (HbA(1c)) and associated metabolic profile remains open to further investigation. |
| 637 | 17300591 | DPP-IV inhibitors such as vildagliptin and sitagliptin have been shown to be highly effective antihyperglycaemic agents that augment insulin secretion and reduce glucagon secretion via glucose-dependent mechanisms. |
| 638 | 17314201 | Transport of the dipeptidyl peptidase-4 inhibitor sitagliptin by human organic anion transporter 3, organic anion transporting polypeptide 4C1, and multidrug resistance P-glycoprotein. |
| 639 | 17314201 | In this report, we demonstrate that sitagliptin is transported by human organic anion transporter hOAT3 (Km=162 microM), organic anion transporting polypeptide OATP4C1, and multidrug resistance (MDR) P-glycoprotein (Pgp), but not by human organic cation transporter 2 hOCT2, hOAT1, oligopeptide transporter hPEPT1, OATP2B1, and the multidrug resistance proteins MRP2 and MRP4. |
| 640 | 17314201 | Our studies suggested that hOAT3, OATP4C1, and MDR1 Pgp might play a role in transporting sitagliptin into and out of renal proximal tubule cells, respectively. |
| 641 | 17314201 | Our data indicate that sitagliptin is unlikely to be a perpetrator of drug-drug interactions with Pgp, hOAT1, or hOAT3 substrates at clinically relevant concentrations. |
| 642 | 17315049 | Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are important incretin hormones contributing to 50-70% of the stimulation of insulin secretion after a meal. |
| 643 | 17315049 | Dipeptidyl-peptidase IV (DPP-4) inhibitors inhibit the degradation of GLP-1 and GIP as well as that of other regulatory peptides. |
| 644 | 17315049 | Like other DPP-4 inhibitors, sitagliptin reduces hemoglobin A1c (HbA1c), fasting and postprandial glucose by glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion. |
| 645 | 17315049 | Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are important incretin hormones contributing to 50-70% of the stimulation of insulin secretion after a meal. |
| 646 | 17315049 | Dipeptidyl-peptidase IV (DPP-4) inhibitors inhibit the degradation of GLP-1 and GIP as well as that of other regulatory peptides. |
| 647 | 17315049 | Like other DPP-4 inhibitors, sitagliptin reduces hemoglobin A1c (HbA1c), fasting and postprandial glucose by glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion. |
| 648 | 17352516 | Sitagliptin, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, improves glycaemic control by inhibiting DPP-4 inactivation of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. |
| 649 | 17352677 | The emergence of glucagon-like peptide 1 (GLP-1) as a well validated approach to the treatment of type 2 diabetes and preclinical validation of dipeptidyl peptidase IV (DPP-4) inhibition as an alternate, oral approach to GLP-1 therapy prompted the initiation of a DPP-4 inhibitor program at Merck in 1999. |
| 650 | 17352677 | The observation that both compounds inhibit the related proline peptidases DPP8 and DPP9 led to the hypothesis that inhibition of DPP8 and/or DPP9 could evoke severe toxicities in preclinical species. |
| 651 | 17352677 | Indeed, the observed toxicities were recapitulated with a selective dual DPP8/9 inhibitor but not with an inhibitor selective for DPP-4. |
| 652 | 17352677 | The emergence of glucagon-like peptide 1 (GLP-1) as a well validated approach to the treatment of type 2 diabetes and preclinical validation of dipeptidyl peptidase IV (DPP-4) inhibition as an alternate, oral approach to GLP-1 therapy prompted the initiation of a DPP-4 inhibitor program at Merck in 1999. |
| 653 | 17352677 | The observation that both compounds inhibit the related proline peptidases DPP8 and DPP9 led to the hypothesis that inhibition of DPP8 and/or DPP9 could evoke severe toxicities in preclinical species. |
| 654 | 17352677 | Indeed, the observed toxicities were recapitulated with a selective dual DPP8/9 inhibitor but not with an inhibitor selective for DPP-4. |
| 655 | 17353295 | The major factors for progressive loss of beta-cell function and mass are glucotoxicity, lipotoxicity, proinflammatory cytokines, leptin, and islet cell amyloid. |
| 656 | 17353295 | The TZDs improve insulin secretory capacity, decrease beta-cell apoptosis, and reduce islet cell amyloid with maintenance of neogenesis. |
| 657 | 17353295 | From the two major incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), only the first one or its mimetics or enhancers can be used for treatment because the diabetic beta-cell is resistant to GIP action. |
| 658 | 17353295 | The acute effect of GLP-1 and GLP-1 receptor agonists on beta-cells is stimulation of glucose-dependent insulin release, followed by enhancement of insulin biosynthesis and stimulation of insulin gene transcription. |
| 659 | 17353295 | The inhibition of the activity of the DPP-IV enzyme enhances endogenous GLP-1 action in vivo, mediated not only by GLP-1 but also by other mediators. |
| 660 | 17371200 | Sitagliptin is a once-daily, orally active, competitive and fully reversible inhibitor of dipeptidyl peptidase 4, the enzyme that is responsible for the rapid degradation of the incretin hormone glucagon-like peptide-1. |
| 661 | 17381073 | Fibroblast activation protein (FAP) and dipeptidyl peptidase-4 (DPP-4) are highly homologous serine proteases of the prolyl peptidase family and therapeutic targets for cancer and diabetes, respectively. |
| 662 | 17381073 | FAP Ala657, which corresponds to DPP-4 Asp663, is important for endopeptidase activity; however, its specific role remains unclear, and it is unknown whether conserved DPP-4 substrate binding residues support FAP endopeptidase activity. |
| 663 | 17381073 | Structural modeling suggests that FAP Ala657 and DPP-4 Asp663 confer their contrasting effects on TSS by modulating the conformation of conserved residues FAP Glu204 and DPP-4 Glu206. |
| 664 | 17381073 | Fibroblast activation protein (FAP) and dipeptidyl peptidase-4 (DPP-4) are highly homologous serine proteases of the prolyl peptidase family and therapeutic targets for cancer and diabetes, respectively. |
| 665 | 17381073 | FAP Ala657, which corresponds to DPP-4 Asp663, is important for endopeptidase activity; however, its specific role remains unclear, and it is unknown whether conserved DPP-4 substrate binding residues support FAP endopeptidase activity. |
| 666 | 17381073 | Structural modeling suggests that FAP Ala657 and DPP-4 Asp663 confer their contrasting effects on TSS by modulating the conformation of conserved residues FAP Glu204 and DPP-4 Glu206. |
| 667 | 17381073 | Fibroblast activation protein (FAP) and dipeptidyl peptidase-4 (DPP-4) are highly homologous serine proteases of the prolyl peptidase family and therapeutic targets for cancer and diabetes, respectively. |
| 668 | 17381073 | FAP Ala657, which corresponds to DPP-4 Asp663, is important for endopeptidase activity; however, its specific role remains unclear, and it is unknown whether conserved DPP-4 substrate binding residues support FAP endopeptidase activity. |
| 669 | 17381073 | Structural modeling suggests that FAP Ala657 and DPP-4 Asp663 confer their contrasting effects on TSS by modulating the conformation of conserved residues FAP Glu204 and DPP-4 Glu206. |
| 670 | 17417933 | Incretin-based therapy, including incretin mimetics such as exenatide and the yet-to-be-approved dipeptidyl peptidase-4 inhibitors, and new basal and inhaled insulin may change the way we currently treat type 2 diabetes. |
| 671 | 17442688 | Plasma levels of parent drug, dipeptidyl peptidase-4 activity, glucose, insulin, and glucagon were measured during 75-g oral glucose tolerance tests performed after an overnight fast, 30 minutes after drug administration. |
| 672 | 17476355 | Diabetes can be a devastating disease, but it can now be treated with nine classes of approved drugs (insulins, sulfonylureas, glinides, biguanides, alpha-glucosidase inhibitors, thiazolidinediones, glucagon-like peptide 1 mimetics, amylin mimetics, and dipeptidyl peptidase 4 inhibitors), in addition to diet and exercise regimens. |
| 673 | 17482289 | DPP-4 inhibition improves glucose tolerance and increases insulin and GLP-1 responses to gastric glucose in association with normalized islet topography in mice with beta-cell-specific overexpression of human islet amyloid polypeptide. |
| 674 | 17482289 | In this study, we explored the effects of DPP-4 inhibition in mice with beta-cell overexpression of human islet amyloid polypeptide (IAPP). |
| 675 | 17482289 | After eight weeks, a gastric tolerance test showed that vildagliptin improved glucose tolerance and markedly (approximately ten-fold) augmented the insulin response in association with augmented (approximately five-fold) levels of intact glucagon-like peptide-1 (GLP-1). |
| 676 | 17482289 | DPP-4 inhibition improves glucose tolerance and increases insulin and GLP-1 responses to gastric glucose in association with normalized islet topography in mice with beta-cell-specific overexpression of human islet amyloid polypeptide. |
| 677 | 17482289 | In this study, we explored the effects of DPP-4 inhibition in mice with beta-cell overexpression of human islet amyloid polypeptide (IAPP). |
| 678 | 17482289 | After eight weeks, a gastric tolerance test showed that vildagliptin improved glucose tolerance and markedly (approximately ten-fold) augmented the insulin response in association with augmented (approximately five-fold) levels of intact glucagon-like peptide-1 (GLP-1). |
| 679 | 17485917 | Since the target of both DPP-IV inhibitors and alpha-glucosidase inhibitors is the lowering of postprandial hyperglycemia, we compared antihyperglycemic effects for E3024 and alpha-glucosidase inhibitors in various oral carbohydrate and meal tolerance tests using normal mice. |
| 680 | 17485917 | This study shows that compared to alpha-glucosidase inhibitors, DPP-IV inhibitors may have more consistent efficacy to reduce postprandial hyperglycemia, independent of the types of carbohydrate contained in a meal, and that the combination of a DPP-IV inhibitor and an alpha-glucosidase inhibitor is expected to be a promising option for lowering postprandial hyperglycemia. |
| 681 | 17485917 | Since the target of both DPP-IV inhibitors and alpha-glucosidase inhibitors is the lowering of postprandial hyperglycemia, we compared antihyperglycemic effects for E3024 and alpha-glucosidase inhibitors in various oral carbohydrate and meal tolerance tests using normal mice. |
| 682 | 17485917 | This study shows that compared to alpha-glucosidase inhibitors, DPP-IV inhibitors may have more consistent efficacy to reduce postprandial hyperglycemia, independent of the types of carbohydrate contained in a meal, and that the combination of a DPP-IV inhibitor and an alpha-glucosidase inhibitor is expected to be a promising option for lowering postprandial hyperglycemia. |
| 683 | 17492130 | Dipeptidyl peptidase IV (DPPIV), which belongs to the prolyl oligopeptidase family of serine proteases, is known to have a variety of regulatory biological functions and has been shown to be implicated in type 2 diabetes. |
| 684 | 17498508 | Biology of incretins: GLP-1 and GIP. |
| 685 | 17498508 | This review focuses on the mechanisms regulating the synthesis, secretion, biological actions, and therapeutic relevance of the incretin peptides glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). |
| 686 | 17498508 | The published literature was reviewed, with emphasis on recent advances in our understanding of the biology of GIP and GLP-1. |
| 687 | 17498508 | GIP and GLP-1 are both secreted within minutes of nutrient ingestion and facilitate the rapid disposal of ingested nutrients. |
| 688 | 17498508 | The rapid degradation of both GIP and GLP-1 by the enzyme dipeptidyl peptidase-4 has led to the development of degradation-resistant GLP-1-receptor agonists and dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes. |
| 689 | 17498508 | GLP-1 and GIP integrate nutrient-derived signals to control food intake, energy absorption, and assimilation. |
| 690 | 17535382 | Management of type 2 diabetes has been improved by the recent introduction of the peroxisome proliferator-activated receptor-gamma agonists and more recently by the incretins including glucagons like peptide analogues and dipeptidyl peptidase-4 inhibitors. |
| 691 | 17543192 | Dipeptidyl peptidase IV is a serine protease with an indirect role in antihyperglycaemia via degradation of the incretin hormones glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide. |
| 692 | 17543192 | In this study, we have investigated upon selectivity of dipeptidyl peptidase IV compared to two other members of the S9b family, dipeptidyl peptidase 8 and 9, based on kinetic analyses of the pancreatic peptide hormones neuropeptide Y and peptide YY. |
| 693 | 17543192 | We report a striking 250-fold preference for cleavage of neuropeptide Y compared to peptide YY observed for DPP-8/-9, but not for DPP-IV. |
| 694 | 17566392 | We here briefly describe the main two proposed approaches : ether to subcutaneously inject an incretinomimetic agent closed to GLP-1 (exenatide) or a long-acting GLP-1 analogue (liraglutide), both being partially resistant to the action of dipeptidylpeptidase-IV (DPP-IV), either to orally administer a selective DPP-IV inhibitor, an enzyme metabolising endogenous GLP-1 (sitagliptin, vildagliptin, .... |
| 695 | 17580730 | Like other DPP-4 inhibitors its action is mediated by increasing levels of the incretin hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP). |
| 696 | 17593274 | Incretin-based therapies with the new classes of glucagon-like peptide-1 mimetics (e.g. exenatide, liraglutide) and dipeptidyl peptidase 4 (DPP-4) inhibitors (e.g. sitagliptin, vildagliptin) may be of particular value in the treatment of overweight/obese type 2 diabetic patients because of their efficacy in improving glycaemic control and their favourable or neutral effects on body weight. |
| 697 | 17593275 | Newer agents based on enhancing incretin activity, including the glucagon-like peptide-1 mimetics exenatide and liraglutide and the oral dipeptidyl peptidase-4 inhibitors sitagliptin and vildagliptin, may offer particular advantages in elderly patients with diabetes. |
| 698 | 17593276 | Dipeptidyl peptidase 4 (DPP-4) inhibition prevents the rapid degradation of the incretins, glucagon-like peptide 1 and glucose-dependent insulinotropic peptide. |
| 699 | 17655515 | Unlike conventional oral antidiabetic agents, these agents promote glucose homeostasis through inhibition of DPP-IV, the enzyme responsible for degradation of two key glucoregulatory hormones: glucagon-like peptide-1 (GLP-1), which extends the action of insulin while also suppressing the release of glucagon, and glucose-dependent insulinotropic peptide (GIP). |
| 700 | 17655515 | Other proposed mechanisms of action of GLP-1 and thus DPP-IV inhibitors include satiety, increased beta-cell production, and inhibition of apoptosis of beta cells. |
| 701 | 17655515 | Clinical studies have evaluated the potential for DPP-IV inhibition to reduce glucagon levels, delay gastric emptying, and stimulate insulin release. |
| 702 | 17655515 | Unlike conventional oral antidiabetic agents, these agents promote glucose homeostasis through inhibition of DPP-IV, the enzyme responsible for degradation of two key glucoregulatory hormones: glucagon-like peptide-1 (GLP-1), which extends the action of insulin while also suppressing the release of glucagon, and glucose-dependent insulinotropic peptide (GIP). |
| 703 | 17655515 | Other proposed mechanisms of action of GLP-1 and thus DPP-IV inhibitors include satiety, increased beta-cell production, and inhibition of apoptosis of beta cells. |
| 704 | 17655515 | Clinical studies have evaluated the potential for DPP-IV inhibition to reduce glucagon levels, delay gastric emptying, and stimulate insulin release. |
| 705 | 17655515 | Unlike conventional oral antidiabetic agents, these agents promote glucose homeostasis through inhibition of DPP-IV, the enzyme responsible for degradation of two key glucoregulatory hormones: glucagon-like peptide-1 (GLP-1), which extends the action of insulin while also suppressing the release of glucagon, and glucose-dependent insulinotropic peptide (GIP). |
| 706 | 17655515 | Other proposed mechanisms of action of GLP-1 and thus DPP-IV inhibitors include satiety, increased beta-cell production, and inhibition of apoptosis of beta cells. |
| 707 | 17655515 | Clinical studies have evaluated the potential for DPP-IV inhibition to reduce glucagon levels, delay gastric emptying, and stimulate insulin release. |
| 708 | 17676345 | Dipeptidyl peptidase IV (DPP-IV) deactivates the incretin hormones GLP-1 and GIP by cleaving the penultimate proline or alanine from the N-terminal (P1-position) of the peptide. |
| 709 | 17703979 | In spite of major advances in the management of type 2 diabetes, and the strictness of new guidelines, some goals remain unachieved and the new family of insulin-secretors (DPP-IV inhibitors, GLP-1 analogues) should enrich therapeutic approaches. |
| 710 | 17704566 | Structural studies of a bifunctional inhibitor of neprilysin and DPP-IV. |
| 711 | 17704566 | Neutral endopeptidase (NEP) is the major enzyme involved in the metabolic inactivation of a number of bioactive peptides including the enkephalins, substance P, endothelin, bradykinin and atrial natriuretic factor, as well as the incretin hormone glucagon-like peptide 1 (GLP-1), which is a potent stimulator of insulin secretion. |
| 712 | 17704566 | The activity of GLP-1 is also rapidly abolished by the serine protease dipeptidyl peptidase IV (DPP-IV), which led to an elevated interest in inhibitors of this enzyme for the treatment of type II diabetes. |
| 713 | 17704566 | Structural studies of a bifunctional inhibitor of neprilysin and DPP-IV. |
| 714 | 17704566 | Neutral endopeptidase (NEP) is the major enzyme involved in the metabolic inactivation of a number of bioactive peptides including the enkephalins, substance P, endothelin, bradykinin and atrial natriuretic factor, as well as the incretin hormone glucagon-like peptide 1 (GLP-1), which is a potent stimulator of insulin secretion. |
| 715 | 17704566 | The activity of GLP-1 is also rapidly abolished by the serine protease dipeptidyl peptidase IV (DPP-IV), which led to an elevated interest in inhibitors of this enzyme for the treatment of type II diabetes. |
| 716 | 17869513 | Substitution at the 1- and 3-positions produced increased selectivity for DPP-4 relative to DPP-8 and DPP-9. |
| 717 | 17877544 | Incretin-based treatment of type 2 diabetes: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. |
| 718 | 17877544 | Activities of the dominant incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide, include glucose-dependent stimulation of insulin secretion and, in preclinical models, improvement in islet beta-cell mass. |
| 719 | 17877544 | Thus, strategies to enhance incretin activity have included development of GLP-1 receptor agonists resistant to the action of DPP-4 (e.g. exenatide and liraglutide) and DPP-4 inhibitors that act to increase concentrations of endogenous intact incretins (e.g. sitagliptin and vildagliptin). |
| 720 | 17877544 | Incretin-based treatment of type 2 diabetes: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. |
| 721 | 17877544 | Activities of the dominant incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide, include glucose-dependent stimulation of insulin secretion and, in preclinical models, improvement in islet beta-cell mass. |
| 722 | 17877544 | Thus, strategies to enhance incretin activity have included development of GLP-1 receptor agonists resistant to the action of DPP-4 (e.g. exenatide and liraglutide) and DPP-4 inhibitors that act to increase concentrations of endogenous intact incretins (e.g. sitagliptin and vildagliptin). |
| 723 | 17904681 | Dipeptidyl peptidase (DPP-IV) rapidly metabolizes hormones such as glucagon-like peptide-1(7-36)amide. |
| 724 | 17904681 | This study evaluated circulating DPP-IV activity in type 2 diabetic patients in relation to GLP-1 degradation and metabolic control. |
| 725 | 17904681 | These data indicate decreased DPP-IV activity and GLP-1 degradation in type 2 diabetes. |
| 726 | 17904681 | Dipeptidyl peptidase (DPP-IV) rapidly metabolizes hormones such as glucagon-like peptide-1(7-36)amide. |
| 727 | 17904681 | This study evaluated circulating DPP-IV activity in type 2 diabetic patients in relation to GLP-1 degradation and metabolic control. |
| 728 | 17904681 | These data indicate decreased DPP-IV activity and GLP-1 degradation in type 2 diabetes. |
| 729 | 17904681 | Dipeptidyl peptidase (DPP-IV) rapidly metabolizes hormones such as glucagon-like peptide-1(7-36)amide. |
| 730 | 17904681 | This study evaluated circulating DPP-IV activity in type 2 diabetic patients in relation to GLP-1 degradation and metabolic control. |
| 731 | 17904681 | These data indicate decreased DPP-IV activity and GLP-1 degradation in type 2 diabetes. |
| 732 | 17909087 | The dipeptidyl peptidase-4 inhibitor vildagliptin improves beta-cell function and insulin sensitivity in subjects with impaired fasting glucose. |
| 733 | 17958029 | The two incretin hormones GLP-1 (Glucagon-Like Peptide-1) and GIP (Glucose-dependent Insulinotropic Peptide) are released by the gut in response to nutrient ingestion. |
| 734 | 17958029 | In addition to its insulinotropic action, GLP-1 (but not GIP) suppresses glucagon secretion, delays gastric emptying and promotes satiety. |
| 735 | 17958029 | Because GLP-1 is rapidly degraded by the ubiquitous enzyme, dipeptidyl peptidase-IV (DPP-IV) and has a very short-lived action, DPP-IV resistant mimetics have been designed. |
| 736 | 17958029 | Several randomized placebo-controlled studies with DPP-IV resistant GLP-1 analogues confirmed their efficacy to improve glycemic control in type 2 diabetic patients. |
| 737 | 17958029 | The two incretin hormones GLP-1 (Glucagon-Like Peptide-1) and GIP (Glucose-dependent Insulinotropic Peptide) are released by the gut in response to nutrient ingestion. |
| 738 | 17958029 | In addition to its insulinotropic action, GLP-1 (but not GIP) suppresses glucagon secretion, delays gastric emptying and promotes satiety. |
| 739 | 17958029 | Because GLP-1 is rapidly degraded by the ubiquitous enzyme, dipeptidyl peptidase-IV (DPP-IV) and has a very short-lived action, DPP-IV resistant mimetics have been designed. |
| 740 | 17958029 | Several randomized placebo-controlled studies with DPP-IV resistant GLP-1 analogues confirmed their efficacy to improve glycemic control in type 2 diabetic patients. |
| 741 | 17981667 | One emerging area of interest is centred upon the actions of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which enhance meal-induced insulin secretion and have trophic effects on the beta-cell. |
| 742 | 17981667 | Two new classes of agents have recently gained regulatory approval for therapy of type 2 diabetes; long-acting stable analogues of GLP-1, the so-called incretin mimetics, and inhibitors of dipeptidyl peptidase 4 (DPP-4, the enzyme responsible for the rapid degradation of the incretin hormones), the so-called incretin enhancers. |
| 743 | 17983555 | GLP-1, also released in a post-prandial manner, promotes insulin production and secretion, reduces glucagon secretion, delays gastric emptying and induces a feeling of fullness. |
| 744 | 17983555 | However the fact that GLP-1 is rapidly degraded by dipeptidylpeptidase IV (DPPIV) in vivo reduces its usefulness. |
| 745 | 17983555 | Thus, in order to improve therapeutic efficacy, two approaches have been investigated: the development of GLP-1 analogs resistant to degradation or the development of DPP-IV inhibitors. |
| 746 | 17983555 | Synthetic analogs of amylin (pramlintide), GLP-1 (exenatide) and inhibitors of the degradation of GLP-1 (sitagliptin, DPP-IV inhibitor) are now available for clinical use. |
| 747 | 17983555 | Promising biological targets being investigated include those leading to insulin sensitization (11beta-HSD-1 inhibitors and antagonists of glucocorticoids receptor), reducing hepatic glucose output (antagonist of glucagon receptor, inhibitors of glycogen phosphorylase and fructose-1,6-biphosphatase) and finally increasing urinary elimination of excess glucose (SGLT inhibitors). |
| 748 | 17983555 | A particular role is played by glucokinase activators (GKA) which can both increase insulin secretion and improve hepatic glucose metabolism. |
| 749 | 17983555 | In this review, we present a summary of the data available on newly approved treatments (amylin and GLP-1 analogs as well as DPP-IV inhibitors) and give an overview of the targets currently being studied for the treatment of type 2 diabetes with an emphasis on the small molecule drug design. |
| 750 | 17983555 | GLP-1, also released in a post-prandial manner, promotes insulin production and secretion, reduces glucagon secretion, delays gastric emptying and induces a feeling of fullness. |
| 751 | 17983555 | However the fact that GLP-1 is rapidly degraded by dipeptidylpeptidase IV (DPPIV) in vivo reduces its usefulness. |
| 752 | 17983555 | Thus, in order to improve therapeutic efficacy, two approaches have been investigated: the development of GLP-1 analogs resistant to degradation or the development of DPP-IV inhibitors. |
| 753 | 17983555 | Synthetic analogs of amylin (pramlintide), GLP-1 (exenatide) and inhibitors of the degradation of GLP-1 (sitagliptin, DPP-IV inhibitor) are now available for clinical use. |
| 754 | 17983555 | Promising biological targets being investigated include those leading to insulin sensitization (11beta-HSD-1 inhibitors and antagonists of glucocorticoids receptor), reducing hepatic glucose output (antagonist of glucagon receptor, inhibitors of glycogen phosphorylase and fructose-1,6-biphosphatase) and finally increasing urinary elimination of excess glucose (SGLT inhibitors). |
| 755 | 17983555 | A particular role is played by glucokinase activators (GKA) which can both increase insulin secretion and improve hepatic glucose metabolism. |
| 756 | 17983555 | In this review, we present a summary of the data available on newly approved treatments (amylin and GLP-1 analogs as well as DPP-IV inhibitors) and give an overview of the targets currently being studied for the treatment of type 2 diabetes with an emphasis on the small molecule drug design. |
| 757 | 17983555 | GLP-1, also released in a post-prandial manner, promotes insulin production and secretion, reduces glucagon secretion, delays gastric emptying and induces a feeling of fullness. |
| 758 | 17983555 | However the fact that GLP-1 is rapidly degraded by dipeptidylpeptidase IV (DPPIV) in vivo reduces its usefulness. |
| 759 | 17983555 | Thus, in order to improve therapeutic efficacy, two approaches have been investigated: the development of GLP-1 analogs resistant to degradation or the development of DPP-IV inhibitors. |
| 760 | 17983555 | Synthetic analogs of amylin (pramlintide), GLP-1 (exenatide) and inhibitors of the degradation of GLP-1 (sitagliptin, DPP-IV inhibitor) are now available for clinical use. |
| 761 | 17983555 | Promising biological targets being investigated include those leading to insulin sensitization (11beta-HSD-1 inhibitors and antagonists of glucocorticoids receptor), reducing hepatic glucose output (antagonist of glucagon receptor, inhibitors of glycogen phosphorylase and fructose-1,6-biphosphatase) and finally increasing urinary elimination of excess glucose (SGLT inhibitors). |
| 762 | 17983555 | A particular role is played by glucokinase activators (GKA) which can both increase insulin secretion and improve hepatic glucose metabolism. |
| 763 | 17983555 | In this review, we present a summary of the data available on newly approved treatments (amylin and GLP-1 analogs as well as DPP-IV inhibitors) and give an overview of the targets currently being studied for the treatment of type 2 diabetes with an emphasis on the small molecule drug design. |
| 764 | 17983555 | GLP-1, also released in a post-prandial manner, promotes insulin production and secretion, reduces glucagon secretion, delays gastric emptying and induces a feeling of fullness. |
| 765 | 17983555 | However the fact that GLP-1 is rapidly degraded by dipeptidylpeptidase IV (DPPIV) in vivo reduces its usefulness. |
| 766 | 17983555 | Thus, in order to improve therapeutic efficacy, two approaches have been investigated: the development of GLP-1 analogs resistant to degradation or the development of DPP-IV inhibitors. |
| 767 | 17983555 | Synthetic analogs of amylin (pramlintide), GLP-1 (exenatide) and inhibitors of the degradation of GLP-1 (sitagliptin, DPP-IV inhibitor) are now available for clinical use. |
| 768 | 17983555 | Promising biological targets being investigated include those leading to insulin sensitization (11beta-HSD-1 inhibitors and antagonists of glucocorticoids receptor), reducing hepatic glucose output (antagonist of glucagon receptor, inhibitors of glycogen phosphorylase and fructose-1,6-biphosphatase) and finally increasing urinary elimination of excess glucose (SGLT inhibitors). |
| 769 | 17983555 | A particular role is played by glucokinase activators (GKA) which can both increase insulin secretion and improve hepatic glucose metabolism. |
| 770 | 17983555 | In this review, we present a summary of the data available on newly approved treatments (amylin and GLP-1 analogs as well as DPP-IV inhibitors) and give an overview of the targets currently being studied for the treatment of type 2 diabetes with an emphasis on the small molecule drug design. |
| 771 | 18020966 | Incretins such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are intestinal hormones that are released in response to ingestion of nutrients, especially carbohydrate. |
| 772 | 18020966 | They have a number of important biological effects, which include release of insulin, inhibition of glucagon and somatostatin, maintenance of beta-cell mass, delay of gastric emptying, and inhibition of feeding. |
| 773 | 18020966 | Incretin metabolism is abnormal in T2D, evidenced by a decreased incretin effect, reduction in nutrient-mediated secretion of GIP and GLP-1 in T2D, and resistance to GIP. |
| 774 | 18020966 | GLP-1, on the other hand, when administered intravenously in T2D is able to increase insulin secretion and improve glucose homeostasis. |
| 775 | 18020966 | As GLP-1 has a very short half-life, due to rapid degradation by the enzyme dipeptidyl peptidase IV (DPPIV), analogues of GIP and GLP-1 that are resistant to the action of DPPIV have been developed and clinical trials have shown their effectiveness. |
| 776 | 18020966 | Strategies to augment the biological actions of GIP and/or GLP-1 in T2D are expected to minimise weight gain, reduce hypoglycaemic episodes and prevent progressive beta-cell failure by increasing beta-cell mass. |
| 777 | 18054732 | The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are physiological gut peptides with insulin-releasing and extrapancreatic glucoregulatory actions. |
| 778 | 18054732 | Incretin analogues/mimetics activate GLP-1 or GIP receptors whilst avoiding physiological inactivation by dipeptidyl peptidase 4 (DPP-4), and they represent one of the newest classes of antidiabetic drug. |
| 779 | 18054732 | This review discusses the various attributes of GLP-1 and GIP for diabetes treatment and summarises current clinical data. |
| 780 | 18054732 | Additionally, it explores the therapeutic possibilities offered by preclinical agents, such as non-peptide GLP-1 mimetics, GLP-1/glucagon hybrid peptides, and specific GIP receptor antagonists. |
| 781 | 18054733 | DPP-4 inhibition prevents the inactivation of glucagon-like peptide 1 (GLP-1), which increases levels of active GLP-1. |
| 782 | 18068977 | Dipeptidyl peptidase-IV (DPP-IV) is an enzyme responsible for the inactivation of the glucoregulatory incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). |
| 783 | 18078308 | DBP-GLP-1 demonstrated superior proteolytic stability against trypsin, intestinal fluid, and the major GLP-1 inactivation enzyme (dipeptidyl peptidase-IV (DPP-IV)) to native GLP-1 or DB-GLP-1 ( p < 0.001). |
| 784 | 18078308 | The in vitro insulinotropic effects of DB-GLP-1 and DBP-GLP-1 showed potent biological activity in a dose-dependent manner, which resembled that of native GLP-1 in terms of stimulating insulin secretion in isolated rat islets of Langerhans. |
| 785 | 18084670 | Glucon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are the incretins which are degraded by dipeptidyl peptidase-4 (DPP-4). |
| 786 | 18084670 | Oral inhibitors of DPP-4 increase GLP-1 levels and this leads to lower glucose levels caused by increased insulin secretion and decreased glucagon levels. |
| 787 | 18084670 | Glucon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are the incretins which are degraded by dipeptidyl peptidase-4 (DPP-4). |
| 788 | 18084670 | Oral inhibitors of DPP-4 increase GLP-1 levels and this leads to lower glucose levels caused by increased insulin secretion and decreased glucagon levels. |
| 789 | 18171434 | The introduction of Glucagon-like peptide-1 (GLP-1) mimetics and dipeptidyl peptidase 4 (DPP-4) inhibitors in treatment of type 2 diabetes will however, to a large extent, influence therapeutic policy. |
| 790 | 18171434 | Thus we suggest that DPP-4 inhibitors or long-acting GLP-1 mimetics will be used as either first-line therapy or as an early addition to metformin. |
| 791 | 18171434 | When patients treated with metformin, sulfonylurea (SU), tiazolidinediones or a combination of these drugs fail, the GLP-1 mimectics may be preferred to insulin treatment. |
| 792 | 18171434 | The introduction of Glucagon-like peptide-1 (GLP-1) mimetics and dipeptidyl peptidase 4 (DPP-4) inhibitors in treatment of type 2 diabetes will however, to a large extent, influence therapeutic policy. |
| 793 | 18171434 | Thus we suggest that DPP-4 inhibitors or long-acting GLP-1 mimetics will be used as either first-line therapy or as an early addition to metformin. |
| 794 | 18171434 | When patients treated with metformin, sulfonylurea (SU), tiazolidinediones or a combination of these drugs fail, the GLP-1 mimectics may be preferred to insulin treatment. |
| 795 | 18174966 | Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are important incretin hormones contributing to 50-70% of the stimulation of insulin secretion after a meal. |
| 796 | 18174966 | Dipeptidyl-peptidase IV (DPP-4) inhibitors inhibit the degradation of GLP-1 and GIP as well as that of other regulatory peptides. |
| 797 | 18174966 | Like other DPP-4 inhibitors, sitagliptin reduces hemoglobin A1c (HbA1c), fasting and postprandial glucose by glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion. |
| 798 | 18174966 | Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are important incretin hormones contributing to 50-70% of the stimulation of insulin secretion after a meal. |
| 799 | 18174966 | Dipeptidyl-peptidase IV (DPP-4) inhibitors inhibit the degradation of GLP-1 and GIP as well as that of other regulatory peptides. |
| 800 | 18174966 | Like other DPP-4 inhibitors, sitagliptin reduces hemoglobin A1c (HbA1c), fasting and postprandial glucose by glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion. |
| 801 | 18201204 | Exendin-4 is a dipeptidyl peptidase IV (DPP-IV)-resistant glucagon-like peptide 1 (GLP-1) mimetic and its synthetic counterpart, exenatide, is being used in the therapy of type 2 diabetes (T2DM). |
| 802 | 18220788 | Extensive research has been carried out world wide on molecular targets for T2DM like PPARgamma, PTP1B, DPP-IV, GSK-3, cannabinoid receptor, fructose-bisphosphatases, beta3 adrenoceptor, etc. in the development of newer anti-diabetic agents. |
| 803 | 18223196 | BI 1356 was >/=10,000-fold more selective for DPP-4 than DPP-8, DPP-9, amino-peptidases N and P, prolyloligopeptidase, trypsin, plasmin, and thrombin and was 90-fold more selective than for fibroblast activation protein in vitro. |
| 804 | 18227398 | Here, we present a corresponding discussion of the newest antihyperglycemic category, modulators of the incretin system, which include the glucagon-like peptide-1 mimetics and the dipeptidyl peptidase-4 inhibitors. |
| 805 | 18357956 | Both GLP-1 agonists and DPP-IV inhibitors may have the ability to expand beta-cell mass. |
| 806 | 18372550 | Sitagliptin (Januvia) is the first selective antagonist of dipeptidylpeptidase-4, an enzyme that degrades glucagon-like peptide-1 (GLP-1). |
| 807 | 18372550 | Sitagliptin increases post-meal insulin secretion ("incretin effect) by enhancing the postprandial GLP-1 response ("incretin enhancer"), in a glucose-dependent manner. |
| 808 | 18375772 | Advancement in the knowledge surrounding the physiology of endogenous glucoregulatory peptide hormones, such as glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, has led to new therapeutic targets for the treatment of type 2 diabetes mellitus. |
| 809 | 18375772 | This article, part 3 of a 3-part series, reviews the new class of medications known as DPP-4 inhibitors as well as discusses a future buccal insulin formulation, Oral-Lyn, on the horizon for the treatment of diabetes mellitus. |
| 810 | 18398599 | They are thought to act by inhibiting the breakdown of glucagon-like peptide-1 and, thereby, selectively enhancing insulin release under conditions when it is physiologically required. |
| 811 | 18398599 | These drugs are selective for DPP-IV, but the enzyme itself has a broad range of substrates other than glucagon-like peptide-1. |
| 812 | 18398599 | Other high affinity substrates of DPP-IV including peptide YY may also play a role in the regulation of energy homeostasis. |
| 813 | 18398599 | The potential role of DPP-IV inhibition on substrates other than glucagon-like peptide-1 in diabetes patients remains to be elucidated. |
| 814 | 18398599 | They are thought to act by inhibiting the breakdown of glucagon-like peptide-1 and, thereby, selectively enhancing insulin release under conditions when it is physiologically required. |
| 815 | 18398599 | These drugs are selective for DPP-IV, but the enzyme itself has a broad range of substrates other than glucagon-like peptide-1. |
| 816 | 18398599 | Other high affinity substrates of DPP-IV including peptide YY may also play a role in the regulation of energy homeostasis. |
| 817 | 18398599 | The potential role of DPP-IV inhibition on substrates other than glucagon-like peptide-1 in diabetes patients remains to be elucidated. |
| 818 | 18398599 | They are thought to act by inhibiting the breakdown of glucagon-like peptide-1 and, thereby, selectively enhancing insulin release under conditions when it is physiologically required. |
| 819 | 18398599 | These drugs are selective for DPP-IV, but the enzyme itself has a broad range of substrates other than glucagon-like peptide-1. |
| 820 | 18398599 | Other high affinity substrates of DPP-IV including peptide YY may also play a role in the regulation of energy homeostasis. |
| 821 | 18398599 | The potential role of DPP-IV inhibition on substrates other than glucagon-like peptide-1 in diabetes patients remains to be elucidated. |
| 822 | 18424366 | Since its discovery glucagon-like peptide-1 (GLP-1) is investigated as a treatment for type II diabetes based on its major function as insulin secretagogue. |
| 823 | 18424366 | Ac-GLP-1-(7-34)-amide may thus have the potential to act as a new long-acting GLP-1 analogue with significant resistance against DPP-IV and retained biological activity in vitro. |
| 824 | 18491437 | The gliptins, a new class of oral drugs for type 2 diabietes mellitus, lower blood glucose levels by a novel mechanism: ie, by inhibiting the enzyme dipeptidyl peptidase 4, thereby increasing the circulating levelsof incretins (gut hormones that can boost insulin levels). |
| 825 | 18525067 | Despite the rapid degradation and inactivation of GLP-1 by the enzyme dipeptidyl peptidase IV (DPP-IV), agents that mimic the actions of GLP-1 are of great clinical interest. |
| 826 | 18525067 | First-in-class IM exenatide, a GLP-1 receptor agonist resistant to DPP-IV inactivation, mimics many beneficial glucoregulatory effects of GLP-1, such as suppressing glucagon secretion, regulating gastric emptying and satiety, and increasing glucose-dependent insulin secretion. |
| 827 | 18525067 | Despite the rapid degradation and inactivation of GLP-1 by the enzyme dipeptidyl peptidase IV (DPP-IV), agents that mimic the actions of GLP-1 are of great clinical interest. |
| 828 | 18525067 | First-in-class IM exenatide, a GLP-1 receptor agonist resistant to DPP-IV inactivation, mimics many beneficial glucoregulatory effects of GLP-1, such as suppressing glucagon secretion, regulating gastric emptying and satiety, and increasing glucose-dependent insulin secretion. |
| 829 | 18535325 | The goal of antidiabetes therapy is to reduce glycosylated hemoglobin (HbA(1c)) levels to prevent or minimize the microvascular complications associated with this disease, such as retinopathy, nephropathy, and neuropathy. |
| 830 | 18535325 | Glycemic control, defined by the American Diabetes Association (ADA) as HbA(1c) <7.0%, is often difficult to achieve despite current treatments, including oral antidiabetes agents, such as biguanides (metformin), sulfonylureas, thiazolidinediones, dipeptidyl peptidase-IV (DPP-IV) inhibitors, meglitinides, and alpha-glucosidase inhibitors, as well as injectable agents, such as glucagon-like peptide-1 (GLP-1) analogues and insulin. |
| 831 | 18561513 | Inhibition of dipeptidyl peptidase-4 (DPP-4) as a novel therapy for type 2 diabetes is based on prevention of the inactivation process of bioactive peptides, the most important in the context of treatment of diabetes of which is glucagon-like peptide-1 (GLP-1). |
| 832 | 18561513 | Both fasting and prandial glucose are reduced by DPP-4 inhibition in combination with metformin in association with improvement of insulin secretion and insulin resistance and increase in concentrations of active GLP-1. |
| 833 | 18561513 | Inhibition of dipeptidyl peptidase-4 (DPP-4) as a novel therapy for type 2 diabetes is based on prevention of the inactivation process of bioactive peptides, the most important in the context of treatment of diabetes of which is glucagon-like peptide-1 (GLP-1). |
| 834 | 18561513 | Both fasting and prandial glucose are reduced by DPP-4 inhibition in combination with metformin in association with improvement of insulin secretion and insulin resistance and increase in concentrations of active GLP-1. |
| 835 | 18600568 | The two incretins glucagon-like peptide-1 (7-36) (GLP-1(7-36)) amide and glucose-dependent insulinotropic peptide (GIP) are released from the small intestine in response to the ingestion of nutrients and regulate glucose homeostasis in a glucose-dependent fashion; however, the action of both incretins is terminated by the rapid N-terminal cleavage of two amino acid residues of GLP-1 and GIP by dipeptidyl peptidase-IV (DPP-IV). |
| 836 | 18600568 | The preservation of active GLP-1 and GIP by inhibiting DPP-IV activity is an attractive strategy for the treatment of diabetes in patients who exhibit a reduced incretin response. |
| 837 | 18600568 | The two incretins glucagon-like peptide-1 (7-36) (GLP-1(7-36)) amide and glucose-dependent insulinotropic peptide (GIP) are released from the small intestine in response to the ingestion of nutrients and regulate glucose homeostasis in a glucose-dependent fashion; however, the action of both incretins is terminated by the rapid N-terminal cleavage of two amino acid residues of GLP-1 and GIP by dipeptidyl peptidase-IV (DPP-IV). |
| 838 | 18600568 | The preservation of active GLP-1 and GIP by inhibiting DPP-IV activity is an attractive strategy for the treatment of diabetes in patients who exhibit a reduced incretin response. |
| 839 | 18640588 | Physiology of incretins (GIP and GLP-1) and abnormalities in type 2 diabetes. |
| 840 | 18640588 | In humans, the incretin effect is mainly caused by two peptide hormones, glucose-dependent insulin releasing polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). |
| 841 | 18640588 | GIP is secreted by K cells from the upper small intestine while GLP-1 is mainly produced in the enteroendocrine L cells located in the distal intestine. |
| 842 | 18640588 | GIP and GLP-1 are both rapidly degraded into inactive metabolites by the enzyme dipeptidyl-peptidase-IV (DPP-IV). |
| 843 | 18640588 | In addition to its effects on insulin secretion, GLP-1 exerts other significant actions, including stimulation of insulin biosynthesis, inhibition of glucagon secretion, inhibition of gastric emptying and acid secretion, reduction of food intake, and trophic effects on the pancreas. |
| 844 | 18640590 | The goal of this review is to think about how to incorporate the GLP-1 based agents, represented by the dipeptidyl peptidase-4 (DPP-4) inhibitors or the glucagon-like peptide-1 (GLP-1) analogs, in the guidelines for the management of type 2 diabetes (T2DM). |
| 845 | 18640590 | Finally, in patients with T2DM inadequately controlled with maximal tolerated oral multi-therapies, GLP-1 agonists are a good alternative to insulin therapy, allowing reaching a better glycaemic control together with a weight loss. |
| 846 | 18640590 | However, for patients who do not tolerate GLP-1 agonist treatment, and for those not reaching the HbA(1c) target, insulin will remain necessary, allowing getting a better metabolic control, with few adverse events. |
| 847 | 18641927 | DPP4 inhibition results in increased blood concentration of the incretin hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP). |
| 848 | 18654064 | The search focused on the newer incretin-based therapies, including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists. |
| 849 | 18654064 | Dipeptidyl peptidase-4 inhibitors exhibit a weight-neutral profile, however, and GLP-1 receptor agonists (eg, exenatide, liraglutide) have achieved significant body weight reductions in spite of improved glycemic control, which is often accompanied by weight gain. |
| 850 | 18654064 | Clinical evidence substantiating the weight-neutral effects of DPP-4 inhibitors and the weight-loss effects of GLP-1 agonists is promising, offering an expansion of therapeutic options for overweight and obese patients with type 2 diabetes mellitus. |
| 851 | 18654064 | The search focused on the newer incretin-based therapies, including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists. |
| 852 | 18654064 | Dipeptidyl peptidase-4 inhibitors exhibit a weight-neutral profile, however, and GLP-1 receptor agonists (eg, exenatide, liraglutide) have achieved significant body weight reductions in spite of improved glycemic control, which is often accompanied by weight gain. |
| 853 | 18654064 | Clinical evidence substantiating the weight-neutral effects of DPP-4 inhibitors and the weight-loss effects of GLP-1 agonists is promising, offering an expansion of therapeutic options for overweight and obese patients with type 2 diabetes mellitus. |
| 854 | 18654064 | The search focused on the newer incretin-based therapies, including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists. |
| 855 | 18654064 | Dipeptidyl peptidase-4 inhibitors exhibit a weight-neutral profile, however, and GLP-1 receptor agonists (eg, exenatide, liraglutide) have achieved significant body weight reductions in spite of improved glycemic control, which is often accompanied by weight gain. |
| 856 | 18654064 | Clinical evidence substantiating the weight-neutral effects of DPP-4 inhibitors and the weight-loss effects of GLP-1 agonists is promising, offering an expansion of therapeutic options for overweight and obese patients with type 2 diabetes mellitus. |
| 857 | 18670111 | Dipeptidyl peptidase IV (DPP-IV) inhibitors have attracted attention as potential drugs for use in the treatment of type 2 diabetes because they prevent the degradation of glucagon-like peptide-1 (GLP-1) and extend its duration of action. |
| 858 | 18722695 | GLP1, a gut hormone secreted in response to meal ingestion, is rapidly degraded by dipeptidylpeptidase-4 (DPP-4). |
| 859 | 18722695 | GLP1 enhances insulin secretion and inhibits glucagon secretion in a glucose-dependent manner, delays gastric emptying and, in animal studies, preserves beta-cell mass by reducing apoptosis and stimulates of beta-cell proliferation. |
| 860 | 18722695 | Two classes of agents based on GLP1 have been launched: DPP-4 inhibitors and DPP-4 resistant GLP1 analogues. |
| 861 | 18722695 | GLP1, a gut hormone secreted in response to meal ingestion, is rapidly degraded by dipeptidylpeptidase-4 (DPP-4). |
| 862 | 18722695 | GLP1 enhances insulin secretion and inhibits glucagon secretion in a glucose-dependent manner, delays gastric emptying and, in animal studies, preserves beta-cell mass by reducing apoptosis and stimulates of beta-cell proliferation. |
| 863 | 18722695 | Two classes of agents based on GLP1 have been launched: DPP-4 inhibitors and DPP-4 resistant GLP1 analogues. |
| 864 | 18769687 | Overview of glucagon-like peptide-1 analogs and dipeptidyl peptidase-4 inhibitors for type 2 diabetes. |
| 865 | 18777503 | It is hypothesized that at the basis of this pathology lies an incretin defect of insulinotropic gut-derived hormones, relying on decreased secretion of GLP-1 (glucagon-like peptide 1), with preserved insulinotropic effect, whereas GIP (glucose-dependent insulinotropic polypeptide) secretion remains within physiological limits, but its action is mostly impaired due to total loss of possibility for stimulation of the second phase insulin secretion. |
| 866 | 18777503 | In the presence of these findings there are many ongoing clinical studies with the use of GLP-1 analogues or GLP-1 receptors activators (GLP-1 agonists), as well as the inhibitors of dipeptidyl peptidase IV (DPP-IV), the enzyme responsible for incretin proteolysis, in the treatment of type 2 diabetes. |
| 867 | 18795210 | Targeting Incretins in Type 2 Diabetes: Role of GLP-1 Receptor Agonists and DPP-4 Inhibitors. |
| 868 | 18795210 | Strategies to leverage the beneficial effects of GLP-1 include GLP-1 receptor agonists or analogs or dipeptidyl peptidase-4 (DPP-4) inhibitors-agents that act by slowing the inactivation of endogenous GLP-1 and GIP. |
| 869 | 18795210 | This review will provide an overview of current and emerging agents that augment the incretin system with a focus on the role of GLP-1 receptor agonists and DPP-4 inhibitors. |
| 870 | 18795210 | Targeting Incretins in Type 2 Diabetes: Role of GLP-1 Receptor Agonists and DPP-4 Inhibitors. |
| 871 | 18795210 | Strategies to leverage the beneficial effects of GLP-1 include GLP-1 receptor agonists or analogs or dipeptidyl peptidase-4 (DPP-4) inhibitors-agents that act by slowing the inactivation of endogenous GLP-1 and GIP. |
| 872 | 18795210 | This review will provide an overview of current and emerging agents that augment the incretin system with a focus on the role of GLP-1 receptor agonists and DPP-4 inhibitors. |
| 873 | 18795210 | Targeting Incretins in Type 2 Diabetes: Role of GLP-1 Receptor Agonists and DPP-4 Inhibitors. |
| 874 | 18795210 | Strategies to leverage the beneficial effects of GLP-1 include GLP-1 receptor agonists or analogs or dipeptidyl peptidase-4 (DPP-4) inhibitors-agents that act by slowing the inactivation of endogenous GLP-1 and GIP. |
| 875 | 18795210 | This review will provide an overview of current and emerging agents that augment the incretin system with a focus on the role of GLP-1 receptor agonists and DPP-4 inhibitors. |
| 876 | 18806525 | Inhibition of the enzyme DPP-IV results in increased activity of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), the incretin hormones. |
| 877 | 18806525 | Through the action of GLP-1 and GIP, DPP-IV inhibitors improve preprandial and postprandial glucose by enhancing insulin secretion and reducing postprandial concentrations of glucagon. |
| 878 | 18806525 | Inhibition of the enzyme DPP-IV results in increased activity of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), the incretin hormones. |
| 879 | 18806525 | Through the action of GLP-1 and GIP, DPP-IV inhibitors improve preprandial and postprandial glucose by enhancing insulin secretion and reducing postprandial concentrations of glucagon. |
| 880 | 18820816 | Incretin mimetics are peptide drugs that mimic several of the actions of glucagon-like peptide-1 (GLP-1) and have been shown to lower glycated hemoglobin (A1C) levels in patients with T2DM. |
| 881 | 18820816 | Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous GLP-1 levels by inhibiting the enzymatic degradation of GLP-1. |
| 882 | 18832295 | Administration of vildagliptin 25 to 200 mg led to rapid and near-complete (>95%) inhibition of DPP-4 activity for at least 4 hours after dosing, which was associated with increases in plasma active glucagon-like peptide-1 of up to 2- to 3-fold compared with placebo. |
| 883 | 18840785 | Inhibition of dipeptidyl peptidase-4 by vildagliptin during glucagon-like Peptide 1 infusion increases liver glucose uptake in the conscious dog. |
| 884 | 18855626 | Glucoregulatory actions of GLP-1 include glucose-dependent enhancement of insulin secretion, inhibition of glucagon secretion, slowing of gastric emptying and reduction of food intake. |
| 885 | 18855626 | GLP-1 is rapidly inactivated by amino peptidase, Dipeptidyl Peptidase-IV (DPP-IV) and the utility of DPP-IV inhibitors are also under investigation. |
| 886 | 18855626 | There is a recent upsurge in the development of GLP-1 mimetics and DPP-IV inhibitors as potential antidiabetic agents. |
| 887 | 18855626 | Glucoregulatory actions of GLP-1 include glucose-dependent enhancement of insulin secretion, inhibition of glucagon secretion, slowing of gastric emptying and reduction of food intake. |
| 888 | 18855626 | GLP-1 is rapidly inactivated by amino peptidase, Dipeptidyl Peptidase-IV (DPP-IV) and the utility of DPP-IV inhibitors are also under investigation. |
| 889 | 18855626 | There is a recent upsurge in the development of GLP-1 mimetics and DPP-IV inhibitors as potential antidiabetic agents. |
| 890 | 18925530 | Diagnostic value of the aminopeptidase N, N-acetyl-beta-D-glucosaminidase and dipeptidylpeptidase IV in evaluating tubular dysfunction in patients with glomerulopathies. |
| 891 | 18929237 | The enzyme DPP-4 cleaves incretins, which, among other functions, stimulate insulin and suppresses glucagon. |
| 892 | 18931099 | Dipeptidyl peptidase-4 inhibition by vildagliptin and the effect on insulin secretion and action in response to meal ingestion in type 2 diabetes. |
| 893 | 18971371 | Chronic treatment with the dipeptidyl peptidase-4 inhibitor BI 1356 [(R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione] increases basal glucagon-like peptide-1 and improves glycemic control in diabetic rodent models. |
| 894 | 18971371 | The effects on HbA1c and GLP-1 were superior to the short-acting DPP-4 inhibitor vildagliptin, demonstrating the potential of BI 1356 as a once daily treatment for type 2 diabetes at low therapeutic doses. |
| 895 | 18971371 | Chronic treatment with the dipeptidyl peptidase-4 inhibitor BI 1356 [(R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione] increases basal glucagon-like peptide-1 and improves glycemic control in diabetic rodent models. |
| 896 | 18971371 | The effects on HbA1c and GLP-1 were superior to the short-acting DPP-4 inhibitor vildagliptin, demonstrating the potential of BI 1356 as a once daily treatment for type 2 diabetes at low therapeutic doses. |
| 897 | 19026584 | Whereas the theoretical benefit of insulin is based on normalization of functional physiology, therapeutic strategies based on GLP-1 aim to increase the circulating concentration of a natural component--the hormone GLP-1. |
| 898 | 19026584 | There are two strategies for increasing GLP-1 plasma concentrations: replace the hormone with a long-acting analogue or molecule with a longer half-life; and prevent its degradation by inhibiting its natural protease, dipeptidyl peptidase IV (DPPIV). |
| 899 | 19038243 | The dipeptidyl peptidase-4 inhibitor alogliptin in combination with pioglitazone improves glycemic control, lipid profiles, and increases pancreatic insulin content in ob/ob mice. |
| 900 | 19038243 | Thus, we evaluated chronic combination therapy with alogliptin, a highly selective dipeptidyl peptidase-4 inhibitor that enhances the action of incretins, and pioglitazone, a thiazolidinedione that improves peripheral and hepatic insulin sensitivity. |
| 901 | 19038243 | After 4-5 weeks of treatment, alogliptin significantly increased plasma active glucagon-like peptide-1 levels up to 4.1-fold and decreased plasma glucagon up to 25%, whereas pioglitazone significantly increased plasma adiponectin up to 1.3-fold. |
| 902 | 19038243 | Combination treatment exhibited a complementary effect, increasing plasma insulin levels by 3.2-fold (alogliptin alone, 1.6-fold; pioglitazone alone, 1.5-fold) and decreasing glycosylated hemoglobin by 2.3% (alogliptin alone, 1.0%; pioglitazone alone, 1.5%), and non-fasting and fasting plasma glucose by 37% and 62% (alogliptin alone, 17% and 24%; pioglitazone alone, 30% and 45%), respectively. |
| 903 | 19038243 | The dipeptidyl peptidase-4 inhibitor alogliptin in combination with pioglitazone improves glycemic control, lipid profiles, and increases pancreatic insulin content in ob/ob mice. |
| 904 | 19038243 | Thus, we evaluated chronic combination therapy with alogliptin, a highly selective dipeptidyl peptidase-4 inhibitor that enhances the action of incretins, and pioglitazone, a thiazolidinedione that improves peripheral and hepatic insulin sensitivity. |
| 905 | 19038243 | After 4-5 weeks of treatment, alogliptin significantly increased plasma active glucagon-like peptide-1 levels up to 4.1-fold and decreased plasma glucagon up to 25%, whereas pioglitazone significantly increased plasma adiponectin up to 1.3-fold. |
| 906 | 19038243 | Combination treatment exhibited a complementary effect, increasing plasma insulin levels by 3.2-fold (alogliptin alone, 1.6-fold; pioglitazone alone, 1.5-fold) and decreasing glycosylated hemoglobin by 2.3% (alogliptin alone, 1.0%; pioglitazone alone, 1.5%), and non-fasting and fasting plasma glucose by 37% and 62% (alogliptin alone, 17% and 24%; pioglitazone alone, 30% and 45%), respectively. |
| 907 | 19061927 | Significant lower VVH7-like immunoreactivity serum level in diabetic patients: evidence for independence from metabolic control and three key enzymes in hemorphin metabolism, cathepsin D, ACE and DPP-IV. |
| 908 | 19061927 | Three enzymatic tests were also applied to determine serum cathepsin D (CD), dipeptidyl peptidase IV (DPP-IV) and angiotensin-converting enzyme (ACE) activities. |
| 909 | 19061927 | An increase of cathepsin D activity was found in serum of diabetic patients compared to controls (0.47 U/ml versus 0.15 U/ml, respectively) whereas DPPIV activity was significantly decreased in diabetic sera (50.81 U/ml versus 282.10 U/l respectively). |
| 910 | 19061927 | Significant lower VVH7-like immunoreactivity serum level in diabetic patients: evidence for independence from metabolic control and three key enzymes in hemorphin metabolism, cathepsin D, ACE and DPP-IV. |
| 911 | 19061927 | Three enzymatic tests were also applied to determine serum cathepsin D (CD), dipeptidyl peptidase IV (DPP-IV) and angiotensin-converting enzyme (ACE) activities. |
| 912 | 19061927 | An increase of cathepsin D activity was found in serum of diabetic patients compared to controls (0.47 U/ml versus 0.15 U/ml, respectively) whereas DPPIV activity was significantly decreased in diabetic sera (50.81 U/ml versus 282.10 U/l respectively). |
| 913 | 19061927 | Significant lower VVH7-like immunoreactivity serum level in diabetic patients: evidence for independence from metabolic control and three key enzymes in hemorphin metabolism, cathepsin D, ACE and DPP-IV. |
| 914 | 19061927 | Three enzymatic tests were also applied to determine serum cathepsin D (CD), dipeptidyl peptidase IV (DPP-IV) and angiotensin-converting enzyme (ACE) activities. |
| 915 | 19061927 | An increase of cathepsin D activity was found in serum of diabetic patients compared to controls (0.47 U/ml versus 0.15 U/ml, respectively) whereas DPPIV activity was significantly decreased in diabetic sera (50.81 U/ml versus 282.10 U/l respectively). |
| 916 | 19065992 | Sitagliptin, the first commercially available dipeptidyl peptidase-4 inhibitor, inhibits the metabolism and inactivation of the incretin hormones GLP-1 and GIP. |
| 917 | 19074620 | GLP-1, on the other hand, is still insulinotropic in T2DM, and this has led to the development of compounds that activate the GLP-1 receptor with a view to improving insulin secretion. |
| 918 | 19074620 | Since 2005, two new classes of drugs based on incretin action have been approved for lowering blood glucose levels in T2DM: an incretin mimetic (exenatide, which is a potent long-acting agonist of the GLP-1 receptor) and an incretin enhancer (sitagliptin, which is a DPP4 inhibitor). |
| 919 | 19128990 | Glucagon-like peptide-1 (GLP-1) analogues and inhibitors of its degrading enzyme, dipeptidyl peptidase IV (DPPIV), are interesting therapy options in human diabetics because they increase insulin secretion and reduce postprandial glucagon secretion. |
| 920 | 19170358 | Besides classical sulfonylureas and glinides, new insulin secretagogues are now available, which target the incretin gut hormone glucagon-like peptide-1 (GLP-1). |
| 921 | 19170358 | Indeed, oral incretin enhancers acting as antagonists of the enzyme DPP-4 (dipeptidylpeptidase-4), which inactivates natural GLP-1,and injectable incretin mimetics (exenatide) or analogues (liraglutide), which reproduce the actions of GLP-1 while resisting to DPP-4, represent new opportunities to stimulate insulin secretion, without increasing the risk of hypoglycaemia and weight gain. |
| 922 | 19179812 | This article reviews data from a number of clinical trials, presentations, and abstracts indicating the importance of the DPP-4 inhibitors sitagliptin, vildagliptin, and alogliptin both alone and in combination with insulin sensitizers in the treatment of type 2 diabetes. |
| 923 | 19179813 | Insulin, glucagon, amylin, the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and other hormones and enzymes interact to maintain glucose homeostasis and normal cellular metabolism. |
| 924 | 19179813 | In addition to reducing HbA1c and fasting plasma glucose, the recently developed diabetes therapies GLP-1 receptor agonists (eg, exenatide, liraglutide) and dipeptidyl peptidase-4 (DPP-4) inhibitors (eg, sitagliptin, vildagliptin) appear to have beneficial effects on beta-cell dysfunction and, possibly, on alpha-cell dysregulation. |
| 925 | 19208898 | Chronic administration of voglibose, an alpha-glucosidase inhibitor, increases active glucagon-like peptide-1 levels by increasing its secretion and decreasing dipeptidyl peptidase-4 activity in ob/ob mice. |
| 926 | 19208898 | Voglibose (0.001 and 0.005%) was administered in the diet to ob/ob mice for 1 day or 3 to 4 weeks to determine effects on incretin profiles and plasma activity of dipeptidyl peptidase-4 (DPP-4), an enzyme responsible for GLP-1 degradation. |
| 927 | 19208898 | Likewise, 1-day treatment with voglibose did not change plasma DPP-4 activity; however, it increased plasma active GLP-1 by 1.6- to 3.4-fold. |
| 928 | 19208898 | A similar treatment with pioglitazone (0.03%), an insulin sensitizer, did not affect plasma DPP-4 activity or GLP-1 levels. |
| 929 | 19208898 | These results suggest that increased GLP-1 secretion, decreased DPP-4 activity, and increased gut GLP-1 content may have contributed to increased active GLP-1 circulation after chronic treatment with voglibose in a glucose control-independent manner in ob/ob mice. |
| 930 | 19208898 | Chronic administration of voglibose, an alpha-glucosidase inhibitor, increases active glucagon-like peptide-1 levels by increasing its secretion and decreasing dipeptidyl peptidase-4 activity in ob/ob mice. |
| 931 | 19208898 | Voglibose (0.001 and 0.005%) was administered in the diet to ob/ob mice for 1 day or 3 to 4 weeks to determine effects on incretin profiles and plasma activity of dipeptidyl peptidase-4 (DPP-4), an enzyme responsible for GLP-1 degradation. |
| 932 | 19208898 | Likewise, 1-day treatment with voglibose did not change plasma DPP-4 activity; however, it increased plasma active GLP-1 by 1.6- to 3.4-fold. |
| 933 | 19208898 | A similar treatment with pioglitazone (0.03%), an insulin sensitizer, did not affect plasma DPP-4 activity or GLP-1 levels. |
| 934 | 19208898 | These results suggest that increased GLP-1 secretion, decreased DPP-4 activity, and increased gut GLP-1 content may have contributed to increased active GLP-1 circulation after chronic treatment with voglibose in a glucose control-independent manner in ob/ob mice. |
| 935 | 19208898 | Chronic administration of voglibose, an alpha-glucosidase inhibitor, increases active glucagon-like peptide-1 levels by increasing its secretion and decreasing dipeptidyl peptidase-4 activity in ob/ob mice. |
| 936 | 19208898 | Voglibose (0.001 and 0.005%) was administered in the diet to ob/ob mice for 1 day or 3 to 4 weeks to determine effects on incretin profiles and plasma activity of dipeptidyl peptidase-4 (DPP-4), an enzyme responsible for GLP-1 degradation. |
| 937 | 19208898 | Likewise, 1-day treatment with voglibose did not change plasma DPP-4 activity; however, it increased plasma active GLP-1 by 1.6- to 3.4-fold. |
| 938 | 19208898 | A similar treatment with pioglitazone (0.03%), an insulin sensitizer, did not affect plasma DPP-4 activity or GLP-1 levels. |
| 939 | 19208898 | These results suggest that increased GLP-1 secretion, decreased DPP-4 activity, and increased gut GLP-1 content may have contributed to increased active GLP-1 circulation after chronic treatment with voglibose in a glucose control-independent manner in ob/ob mice. |
| 940 | 19208898 | Chronic administration of voglibose, an alpha-glucosidase inhibitor, increases active glucagon-like peptide-1 levels by increasing its secretion and decreasing dipeptidyl peptidase-4 activity in ob/ob mice. |
| 941 | 19208898 | Voglibose (0.001 and 0.005%) was administered in the diet to ob/ob mice for 1 day or 3 to 4 weeks to determine effects on incretin profiles and plasma activity of dipeptidyl peptidase-4 (DPP-4), an enzyme responsible for GLP-1 degradation. |
| 942 | 19208898 | Likewise, 1-day treatment with voglibose did not change plasma DPP-4 activity; however, it increased plasma active GLP-1 by 1.6- to 3.4-fold. |
| 943 | 19208898 | A similar treatment with pioglitazone (0.03%), an insulin sensitizer, did not affect plasma DPP-4 activity or GLP-1 levels. |
| 944 | 19208898 | These results suggest that increased GLP-1 secretion, decreased DPP-4 activity, and increased gut GLP-1 content may have contributed to increased active GLP-1 circulation after chronic treatment with voglibose in a glucose control-independent manner in ob/ob mice. |
| 945 | 19208898 | Chronic administration of voglibose, an alpha-glucosidase inhibitor, increases active glucagon-like peptide-1 levels by increasing its secretion and decreasing dipeptidyl peptidase-4 activity in ob/ob mice. |
| 946 | 19208898 | Voglibose (0.001 and 0.005%) was administered in the diet to ob/ob mice for 1 day or 3 to 4 weeks to determine effects on incretin profiles and plasma activity of dipeptidyl peptidase-4 (DPP-4), an enzyme responsible for GLP-1 degradation. |
| 947 | 19208898 | Likewise, 1-day treatment with voglibose did not change plasma DPP-4 activity; however, it increased plasma active GLP-1 by 1.6- to 3.4-fold. |
| 948 | 19208898 | A similar treatment with pioglitazone (0.03%), an insulin sensitizer, did not affect plasma DPP-4 activity or GLP-1 levels. |
| 949 | 19208898 | These results suggest that increased GLP-1 secretion, decreased DPP-4 activity, and increased gut GLP-1 content may have contributed to increased active GLP-1 circulation after chronic treatment with voglibose in a glucose control-independent manner in ob/ob mice. |
| 950 | 19217455 | A single administration of ASP8497 and vildagliptin significantly improved glucose tolerance by increasing plasma insulin and glucagon-like peptide-1 levels. |
| 951 | 19217455 | After 1 week of chronic daily dosing, the DPP-IV inhibitors caused a significant improvement in glucose tolerance similar to those observed on day 1 by increasing the plasma insulin and glucagon-like peptide-1 levels. |
| 952 | 19217790 | DPP-4, a protease that specifically cleaves dipeptides from proteins and oligopeptides after a penultimate N-terminal proline or alanine, is involved in the degradation of a number of neuropeptides, peptide hormones and cytokines, including the incretins GLP-1 and GIP. |
| 953 | 19217790 | As soon as released from the gut in response to food intake, GLP-1 and GIP exert a potent glucose-dependent insulinotropic action, thereby playing a key role in the maintenance of post-meal glycemic control. |
| 954 | 19217790 | Consequently, inhibiting DPP-4 prolongs the action of GLP-1 and GIP, which in turn improves glucose homeostasis with a low risk of hypoglycemia and potential for disease modification. |
| 955 | 19217790 | Achieving desired selectivity for DPP-4 over other related peptidases such as DPP-8 and DPP-9 (inhibition of which was linked to toxicity in animal studies) and long-acting potential for maximal efficacy (particularly in more severe diabetic patients) were the major challenges. |
| 956 | 19217790 | DPP-4, a protease that specifically cleaves dipeptides from proteins and oligopeptides after a penultimate N-terminal proline or alanine, is involved in the degradation of a number of neuropeptides, peptide hormones and cytokines, including the incretins GLP-1 and GIP. |
| 957 | 19217790 | As soon as released from the gut in response to food intake, GLP-1 and GIP exert a potent glucose-dependent insulinotropic action, thereby playing a key role in the maintenance of post-meal glycemic control. |
| 958 | 19217790 | Consequently, inhibiting DPP-4 prolongs the action of GLP-1 and GIP, which in turn improves glucose homeostasis with a low risk of hypoglycemia and potential for disease modification. |
| 959 | 19217790 | Achieving desired selectivity for DPP-4 over other related peptidases such as DPP-8 and DPP-9 (inhibition of which was linked to toxicity in animal studies) and long-acting potential for maximal efficacy (particularly in more severe diabetic patients) were the major challenges. |
| 960 | 19217790 | DPP-4, a protease that specifically cleaves dipeptides from proteins and oligopeptides after a penultimate N-terminal proline or alanine, is involved in the degradation of a number of neuropeptides, peptide hormones and cytokines, including the incretins GLP-1 and GIP. |
| 961 | 19217790 | As soon as released from the gut in response to food intake, GLP-1 and GIP exert a potent glucose-dependent insulinotropic action, thereby playing a key role in the maintenance of post-meal glycemic control. |
| 962 | 19217790 | Consequently, inhibiting DPP-4 prolongs the action of GLP-1 and GIP, which in turn improves glucose homeostasis with a low risk of hypoglycemia and potential for disease modification. |
| 963 | 19217790 | Achieving desired selectivity for DPP-4 over other related peptidases such as DPP-8 and DPP-9 (inhibition of which was linked to toxicity in animal studies) and long-acting potential for maximal efficacy (particularly in more severe diabetic patients) were the major challenges. |
| 964 | 19227470 | Changes in the myocardial capillary network were examined using the double-staining enzymatic method for alkaline phosphatase (AP) and dipeptidylpeptidase IV (DPPIV) This method allows the identification of the arteriolar (AP-containing) and the venular (DPPIV-containing) portions of the capillary network. |
| 965 | 19273123 | Thiazolidinediones activate PPAR-gamma and improve hepatic insulin sensitivity, primarily through indirect effects on lipid metabolism. |
| 966 | 19273123 | Incretins, incretin mimetics, and dipeptidyl peptidase-4 inhibitors reduce postprandial hepatic glucose production by increasing insulin secretion and limiting glucagon release, as well as through possible direct effects on the liver. |
| 967 | 19275548 | The two key hormones responsible are named glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). |
| 968 | 19275548 | The other group comprises the gliptins (e.g. sitagliptin and vildagliptin) which boost endogenous incretin activity by inhibiting the enzyme dipeptidyl peptidase 4 (DPP 4) that degrades both GLP-1 and GIP. |
| 969 | 19275672 | This review article focuses on the therapeutic potential of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), in treating type 2 diabetes mellitus (T2DM). |
| 970 | 19275672 | Therefore, the actions of GLP-1 and GIP, which include potentation of meal-induced insulin secretion and trophic effects on the beta-cell, have attracted a lot of interest. |
| 971 | 19275672 | Two new drug classes based on the actions of the incretin hormones have recently been approved for therapy of T2DM; injectable long-acting stable analogues of GLP-1, incretin mimetics, and orally available inhibitors of dipeptidyl peptidase 4 (DPP4; the enzyme responsible for the rapid degradation of GLP-1 and GIP), the so-called incretin enhancers. |
| 972 | 19288260 | By inhibiting the dipeptidyl peptidase-4 (DPP-4) enzyme, vildagliptin raises the levels of the active incretin hormones, glucagon-like peptide 1 and glucose-dependent insulinotropic peptide. |
| 973 | 19330494 | These can mainly be divided into two broad categories; GLP-1 agonists/analogs (exenatide, liraglutide), and dipeptidyl peptidase-4 (DPP-4; the enzyme responsible for rapid inactivation of incretins) inhibitors (sitagliptin, vildagliptin). |
| 974 | 19330494 | Current data suggest that saxagliptin as monotherapy or in combination with metformin, glyburide, or a glitazone results in significant reductions in fasting and postprandial plasma glucose and hemoglobin A(1c) (HbA(1c)). |
| 975 | 19361194 | We assessed the receptor binding affinity and cAMP production activity in vitro, the proteolytic resistance against dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) 24.11, and the blood glucose-lowering activity in diabetic db/db mice. |
| 976 | 19361194 | Addition of sialyl LacNAc to GLP-1 greatly improved stability against DPP-IV and NEP 24.11 as compared to the native type. |
| 977 | 19361194 | In addition, the stability of GLP-1 against both DPP-IV and NEP24.11 incrementally improved with an increase in the content of sialyl LacNAc in the peptide. |
| 978 | 19361194 | We assessed the receptor binding affinity and cAMP production activity in vitro, the proteolytic resistance against dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) 24.11, and the blood glucose-lowering activity in diabetic db/db mice. |
| 979 | 19361194 | Addition of sialyl LacNAc to GLP-1 greatly improved stability against DPP-IV and NEP 24.11 as compared to the native type. |
| 980 | 19361194 | In addition, the stability of GLP-1 against both DPP-IV and NEP24.11 incrementally improved with an increase in the content of sialyl LacNAc in the peptide. |
| 981 | 19361194 | We assessed the receptor binding affinity and cAMP production activity in vitro, the proteolytic resistance against dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) 24.11, and the blood glucose-lowering activity in diabetic db/db mice. |
| 982 | 19361194 | Addition of sialyl LacNAc to GLP-1 greatly improved stability against DPP-IV and NEP 24.11 as compared to the native type. |
| 983 | 19361194 | In addition, the stability of GLP-1 against both DPP-IV and NEP24.11 incrementally improved with an increase in the content of sialyl LacNAc in the peptide. |
| 984 | 19365392 | This is evident from the recent success of glucagon-like peptide 1 (GLP1) mimetics and dipeptidyl peptidase 4 (DPP4) inhibitors, which promote activation of the GLP1 receptor to stimulate insulin secretion and inhibit glucagon secretion, and also have the potential to increase beta-cell mass. |
| 985 | 19365392 | Other islet beta-cell GPCRs that are involved in the regulation of islet function include the glucose-dependent insulinotropic peptide (GIP) receptor, lipid GPCRs, pleiotropic peptide GPCRs and islet biogenic amine GPCRs. |
| 986 | 19418936 | Vildagliptin (Galvus) is a selective inhibitor of dipeptidylpeptidase-4, an enzyme involved in the metabolism of glucagon-like peptide-1 (GLP-1) secreted by L cells of the intestine. |
| 987 | 19418936 | It potentiates the insulin secretory response (incretin effect) by enhancing the endogenous post-prandial response of GLP-1 (incretin enhancer) in a glucose-dependent manner. |
| 988 | 19421968 | A MEDLINE search using the terms "GLP-1" (ie, glucagon-like peptide 1), "incretins," "exenatide," and "DPP-IV inhibitors" (ie, dipeptidyl peptidase IV inhibitors) was performed, and pertinent articles from the past 10 years were reviewed. |
| 989 | 19444259 | Incretin-based drugs, such as glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors, are now routinely used to treat type 2 diabetes mellitus. |
| 990 | 19444259 | These agents regulate glucose metabolism through multiple mechanisms, their use is associated with low rates of hypoglycemia, and they either do not affect body weight (dipeptidyl peptidase 4 inhibitors), or promote weight loss (glucagon-like peptide-1 receptor agonists). |
| 991 | 19444259 | Incretin-based drugs, such as glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors, are now routinely used to treat type 2 diabetes mellitus. |
| 992 | 19444259 | These agents regulate glucose metabolism through multiple mechanisms, their use is associated with low rates of hypoglycemia, and they either do not affect body weight (dipeptidyl peptidase 4 inhibitors), or promote weight loss (glucagon-like peptide-1 receptor agonists). |
| 993 | 19464424 | This article aims to provide an overview of efficacy and safety data on glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes mellitus. |
| 994 | 19464424 | Our goal is to differentiate the clinical profiles of GLP-1 receptor agonists and DPP-4 inhibitors, as well as the individual agents within each class. |
| 995 | 19464424 | Additionally, we examine the utility of GLP-1 receptor agonists and DPP-4 inhibitors as these agents may be applied at different stages of type 2 diabetes therapy and discuss recently published clinical findings and their implications for treatment. |
| 996 | 19464424 | This article aims to provide an overview of efficacy and safety data on glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes mellitus. |
| 997 | 19464424 | Our goal is to differentiate the clinical profiles of GLP-1 receptor agonists and DPP-4 inhibitors, as well as the individual agents within each class. |
| 998 | 19464424 | Additionally, we examine the utility of GLP-1 receptor agonists and DPP-4 inhibitors as these agents may be applied at different stages of type 2 diabetes therapy and discuss recently published clinical findings and their implications for treatment. |
| 999 | 19464424 | This article aims to provide an overview of efficacy and safety data on glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes mellitus. |
| 1000 | 19464424 | Our goal is to differentiate the clinical profiles of GLP-1 receptor agonists and DPP-4 inhibitors, as well as the individual agents within each class. |
| 1001 | 19464424 | Additionally, we examine the utility of GLP-1 receptor agonists and DPP-4 inhibitors as these agents may be applied at different stages of type 2 diabetes therapy and discuss recently published clinical findings and their implications for treatment. |
| 1002 | 19464426 | The key endogenous hormones of incretin system are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1); a key enzymatic regulator of these hormones is dipeptidyl peptidase-4, which rapidly inactivates/degrades the incretin hormones. |
| 1003 | 19482472 | The inhibitors show good to moderate biochemical potency against DPP4 and display distinct selectivity profiles towards DPP7, DPP8 and DPP9 depending on their substitution. |
| 1004 | 19520592 | Constitutive increase in active GLP-1 levels by the DPP4 inhibitor ASP4000 on a new meal tolerance test in Zucker fatty rats. |
| 1005 | 19520592 | Glucagon-like peptide-1 (GLP-1), an incretin hormone, is essential for the regulation of insulin secretion and glucose homeostasis. |
| 1006 | 19520592 | GLP-1 is rapidly degraded by dipeptidyl peptidase 4 (DPP4); therefore, DPP4 inhibitors are considered to be a novel class of oral antihyperglycemic agents. |
| 1007 | 19520592 | Normally, oral glucose tolerance tests are used for evalating glucose-lowering efficacy, but the augmentation of active GLP-1 via DPP4 inhibition in this test was transient. |
| 1008 | 19520592 | ASP4000 is an orally effective inhibitor of DPP4 that greatly augments meal-stimulated circulating levels of active GLP-1 constitutively and improves hyperglycemia. |
| 1009 | 19520592 | Our new meal tolerance test is useful for evaluating postprandial hyperglycemia and could be an excellent model for studying the secretion of active GLP-1 via the inhibition of DPP4. |
| 1010 | 19520592 | Constitutive increase in active GLP-1 levels by the DPP4 inhibitor ASP4000 on a new meal tolerance test in Zucker fatty rats. |
| 1011 | 19520592 | Glucagon-like peptide-1 (GLP-1), an incretin hormone, is essential for the regulation of insulin secretion and glucose homeostasis. |
| 1012 | 19520592 | GLP-1 is rapidly degraded by dipeptidyl peptidase 4 (DPP4); therefore, DPP4 inhibitors are considered to be a novel class of oral antihyperglycemic agents. |
| 1013 | 19520592 | Normally, oral glucose tolerance tests are used for evalating glucose-lowering efficacy, but the augmentation of active GLP-1 via DPP4 inhibition in this test was transient. |
| 1014 | 19520592 | ASP4000 is an orally effective inhibitor of DPP4 that greatly augments meal-stimulated circulating levels of active GLP-1 constitutively and improves hyperglycemia. |
| 1015 | 19520592 | Our new meal tolerance test is useful for evaluating postprandial hyperglycemia and could be an excellent model for studying the secretion of active GLP-1 via the inhibition of DPP4. |
| 1016 | 19520592 | Constitutive increase in active GLP-1 levels by the DPP4 inhibitor ASP4000 on a new meal tolerance test in Zucker fatty rats. |
| 1017 | 19520592 | Glucagon-like peptide-1 (GLP-1), an incretin hormone, is essential for the regulation of insulin secretion and glucose homeostasis. |
| 1018 | 19520592 | GLP-1 is rapidly degraded by dipeptidyl peptidase 4 (DPP4); therefore, DPP4 inhibitors are considered to be a novel class of oral antihyperglycemic agents. |
| 1019 | 19520592 | Normally, oral glucose tolerance tests are used for evalating glucose-lowering efficacy, but the augmentation of active GLP-1 via DPP4 inhibition in this test was transient. |
| 1020 | 19520592 | ASP4000 is an orally effective inhibitor of DPP4 that greatly augments meal-stimulated circulating levels of active GLP-1 constitutively and improves hyperglycemia. |
| 1021 | 19520592 | Our new meal tolerance test is useful for evaluating postprandial hyperglycemia and could be an excellent model for studying the secretion of active GLP-1 via the inhibition of DPP4. |
| 1022 | 19520592 | Constitutive increase in active GLP-1 levels by the DPP4 inhibitor ASP4000 on a new meal tolerance test in Zucker fatty rats. |
| 1023 | 19520592 | Glucagon-like peptide-1 (GLP-1), an incretin hormone, is essential for the regulation of insulin secretion and glucose homeostasis. |
| 1024 | 19520592 | GLP-1 is rapidly degraded by dipeptidyl peptidase 4 (DPP4); therefore, DPP4 inhibitors are considered to be a novel class of oral antihyperglycemic agents. |
| 1025 | 19520592 | Normally, oral glucose tolerance tests are used for evalating glucose-lowering efficacy, but the augmentation of active GLP-1 via DPP4 inhibition in this test was transient. |
| 1026 | 19520592 | ASP4000 is an orally effective inhibitor of DPP4 that greatly augments meal-stimulated circulating levels of active GLP-1 constitutively and improves hyperglycemia. |
| 1027 | 19520592 | Our new meal tolerance test is useful for evaluating postprandial hyperglycemia and could be an excellent model for studying the secretion of active GLP-1 via the inhibition of DPP4. |
| 1028 | 19520592 | Constitutive increase in active GLP-1 levels by the DPP4 inhibitor ASP4000 on a new meal tolerance test in Zucker fatty rats. |
| 1029 | 19520592 | Glucagon-like peptide-1 (GLP-1), an incretin hormone, is essential for the regulation of insulin secretion and glucose homeostasis. |
| 1030 | 19520592 | GLP-1 is rapidly degraded by dipeptidyl peptidase 4 (DPP4); therefore, DPP4 inhibitors are considered to be a novel class of oral antihyperglycemic agents. |
| 1031 | 19520592 | Normally, oral glucose tolerance tests are used for evalating glucose-lowering efficacy, but the augmentation of active GLP-1 via DPP4 inhibition in this test was transient. |
| 1032 | 19520592 | ASP4000 is an orally effective inhibitor of DPP4 that greatly augments meal-stimulated circulating levels of active GLP-1 constitutively and improves hyperglycemia. |
| 1033 | 19520592 | Our new meal tolerance test is useful for evaluating postprandial hyperglycemia and could be an excellent model for studying the secretion of active GLP-1 via the inhibition of DPP4. |
| 1034 | 19579179 | Inhibition of neutral endopeptidase 24.11 does not potentiate the improvement in glycemic control obtained with dipeptidyl peptidase-4 inhibition in diabetic Goto-Kakizaki rats. |
| 1035 | 19580949 | The key endogenous hormones of incretin system are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1); a key enzymatic regulator of these hormones is dipeptidyl peptidase-4, which rapidly inactivates/degrades the incretin hormones. |
| 1036 | 19580950 | This article aims to provide an overview of efficacy and safety data on glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes mellitus. |
| 1037 | 19580950 | Our goal is to differentiate the clinical profiles of GLP-1 receptor agonists and DPP-4 inhibitors, as well as the individual agents within each class. |
| 1038 | 19580950 | Additionally, we examine the utility of GLP-1 receptor agonists and DPP-4 inhibitors as these agents may be applied at different stages of type 2 diabetes therapy and discuss recently published clinical findings and their implications for treatment. |
| 1039 | 19580950 | This article aims to provide an overview of efficacy and safety data on glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes mellitus. |
| 1040 | 19580950 | Our goal is to differentiate the clinical profiles of GLP-1 receptor agonists and DPP-4 inhibitors, as well as the individual agents within each class. |
| 1041 | 19580950 | Additionally, we examine the utility of GLP-1 receptor agonists and DPP-4 inhibitors as these agents may be applied at different stages of type 2 diabetes therapy and discuss recently published clinical findings and their implications for treatment. |
| 1042 | 19580950 | This article aims to provide an overview of efficacy and safety data on glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes mellitus. |
| 1043 | 19580950 | Our goal is to differentiate the clinical profiles of GLP-1 receptor agonists and DPP-4 inhibitors, as well as the individual agents within each class. |
| 1044 | 19580950 | Additionally, we examine the utility of GLP-1 receptor agonists and DPP-4 inhibitors as these agents may be applied at different stages of type 2 diabetes therapy and discuss recently published clinical findings and their implications for treatment. |
| 1045 | 19689275 | Since implicated in the regulation of the biological activity of hormones and chemokines, such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, DPP4 inhibition offers a new potential therapeutic approach for type 2 diabetes mellitus, as monotherapy and adjunct therapy to other oral agents. |
| 1046 | 19689275 | The clinical use of presently available orally active inhibitors of DPP4, however, has been associated with side effects that have been in part attributed to the inhibition of related serine proteases, such as DPP8 and DPP9. |
| 1047 | 19689275 | Since implicated in the regulation of the biological activity of hormones and chemokines, such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, DPP4 inhibition offers a new potential therapeutic approach for type 2 diabetes mellitus, as monotherapy and adjunct therapy to other oral agents. |
| 1048 | 19689275 | The clinical use of presently available orally active inhibitors of DPP4, however, has been associated with side effects that have been in part attributed to the inhibition of related serine proteases, such as DPP8 and DPP9. |
| 1049 | 19707284 | The low risk of hypoglycemia, and beneficial or neutral effects on body weight, render GLP-1 agonists and DPP-4 inhibitors suitable alternatives to insulin secretagogues and insulin in overweight and elderly patients. |
| 1050 | 19743938 | These drugs include the glucagon-like peptide (GLP-1) agonists, exenatide, and dipeptidyl peptidase (DPP-IV) inhibitors such as sitagliptin and saxagliptin. |
| 1051 | 19748062 | Mechanisms underlying the rapid degradation and elimination of the incretin hormones GLP-1 and GIP. |
| 1052 | 19748062 | The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP, gastric inhibitory peptide) are secreted from intestinal L and K cells and stimulate insulin secretion from pancreatic beta cells. |
| 1053 | 19748062 | However, they are immediately inactivated mainly via N-terminal degradation by dipeptidyl peptidase IV (DPP IV, CD26), a specialised enzyme located on the cell surface enzyme of endothelial, epithelial and some other cell types. |
| 1054 | 19748065 | Dipeptidyl-peptidase IV (DPP-4) inhibitors inhibit the degradation of the incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). |
| 1055 | 19748066 | DPP-4 inhibition increases insulin secretion and reduces glucagon secretion by preventing the inactivation of glucagon-like peptide-1 (GLP-1), thereby lowering glucose levels. |
| 1056 | 19777398 | The inhibition of DPP-4 by linagliptin was also demonstrated in vivo, resulting in increased glucagon-like peptide 1 levels and improved glucose tolerance in both healthy animals and models of disease. |
| 1057 | 19791828 | Saxagliptin and its active metabolite M2 are dipeptidyl peptidase-4 inhibitors that improve glycaemic control by preventing the inactivation of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. |
| 1058 | 19791828 | This increases GLP-1 levels, stimulates insulin secretion and reduces postprandial glucagon and glucose levels. |
| 1059 | 19806507 | Albiglutide, an albumin-based fusion of glucagon-like peptide 1 for the potential treatment of type 2 diabetes. |
| 1060 | 19806507 | Albiglutide has a longer half-life as a result of its fusion with albumin and its resistance to degradation by DPP-4, caused by an amino acid substitution (Ala to Glu) at the DPP-4-sensitive hydrolysis site. |
| 1061 | 19817800 | Recently, glucagon-like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-IV (DPP-IV) inhibitors have been developed as new antidiabetic drugs. |
| 1062 | 19817800 | Until recently, cAMP was generally thought to potentiate insulin secretion through protein kinase A (PKA) phosphorylation of proteins associated with the secretory process. |
| 1063 | 19819973 | Neurogenin 3-specific dipeptidyl peptidase-2 deficiency causes impaired glucose tolerance, insulin resistance, and visceral obesity. |
| 1064 | 19819973 | We generated mice with a neurogenin 3 (NGN3)-specific DPP2 knockdown (kd) to explore a possible role of DPP2 in maintaining metabolic homeostasis. |
| 1065 | 19819973 | Interestingly, the phenotype of NGN3-DPP2 kd mice is opposite that of DPP4 knockout mice with regard to glucose metabolism, namely the former have normal glucagon-like peptide 1 levels but present with glucose intolerance, whereas the latter have increased glucagon-like peptide 1, which is accompanied by augmented glucose tolerance. |
| 1066 | 19820276 | The incretin-based therapies, such as the glucagon-like peptide-1 (GLP-1) receptor agonists and the dipeptidyl peptidase-4 inhibitors, have been shown to be safe and effective in lowering glucose while eliciting favorable effects on weight (ie, weight-reducing and weight-neutral, respectively). |
| 1067 | 19820278 | Among the newer agents, the dipeptidyl peptidase-4 inhibitors generally are weight-neutral in addition to lowering glucose, while the glucagon-like peptide-1 receptor agonists lead to weight reduction. |
| 1068 | 19830675 | Six different classes of agents are available: Biguanides, sulfonylureas, glinides, glitazones, alpha-glucosidase inhibitors and dipeptidyl peptidase-4 inhibitors. |
| 1069 | 19837468 | Dipeptidyl peptidase (DPP)-4 is a member of the S9b serine protease family, which also includes DPP8 and DPP9. |
| 1070 | 19837468 | Recent data suggest that the early DPP4-specific inhibitors might also bind DPP8 and DPP9, thus exerting their effects through non-specific binding. |
| 1071 | 19858063 | We consider monotherapy, dual therapy, and triple therapy, including 8 major classes of medications (biguanides, dipeptidyl-peptidase-4 inhibitors, incretin mimetics, thiazolidinediones, alpha-glucosidase inhibitors, sulfonylureas, meglitinides, and bile acid sequestrants) and insulin therapy (basal, premixed, and multiple daily injections), with or without orally administered medications. |
| 1072 | 19878257 | Glucagon-like peptide-1 (GLP-1) is an incretin hormone that is known to stimulate glucose-dependent insulin secretion. |
| 1073 | 19878257 | However, GLP-1 is rapidly degraded by dipeptidyl peptidase-4 (DPP-4), which limits the clinical relevance of GLP-1 for the treatment of type 2 diabetes. |
| 1074 | 19878257 | Two main classes of GLP-1-based therapies have now been developed: DPP-4 inhibitors and GLP-1 receptor agonists. |
| 1075 | 19878257 | Glucagon-like peptide-1 (GLP-1) is an incretin hormone that is known to stimulate glucose-dependent insulin secretion. |
| 1076 | 19878257 | However, GLP-1 is rapidly degraded by dipeptidyl peptidase-4 (DPP-4), which limits the clinical relevance of GLP-1 for the treatment of type 2 diabetes. |
| 1077 | 19878257 | Two main classes of GLP-1-based therapies have now been developed: DPP-4 inhibitors and GLP-1 receptor agonists. |
| 1078 | 19894195 | Progress in the catalytic asymmetric hydrogenation and amination of unprotected substrates has enabled the establishment of concise synthetic routes for the production of the potent dipeptidyl peptidase 4 inhibitor sitagliptin, and the aldose reductase inhibitor ranirestat (Dainippon Sumimoto Pharma Co Ltd/Eisai Co Ltd/ Kyorin Pharmaceutical Co Ltd), both of which have attracted particular attention for their potential to treat T2DM and diabetic complications, respectively. |
| 1079 | 19940419 | Incretin-based therapy is either delivered orally (dipeptidyl peptidase-4 [DPP-4]) inhibitors or injected subcutaneously (glucagon-like peptide-1 [GLP-1] mimetics and analogues). |
| 1080 | 19940419 | Dipeptidyl peptidase-4 inhibitors are effective either as a single or combination therapy in lowering glycated hemoglobin, fasting and postprandial glucose levels, with a low incidence of hypoglycemia and no weight gain. |
| 1081 | 19940419 | Incretin-based therapy is either delivered orally (dipeptidyl peptidase-4 [DPP-4]) inhibitors or injected subcutaneously (glucagon-like peptide-1 [GLP-1] mimetics and analogues). |
| 1082 | 19940419 | Dipeptidyl peptidase-4 inhibitors are effective either as a single or combination therapy in lowering glycated hemoglobin, fasting and postprandial glucose levels, with a low incidence of hypoglycemia and no weight gain. |
| 1083 | 19947814 | The incretin effect, mediated by glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), plays an important role in the regulation of insulin secretion in response to oral glucose. |
| 1084 | 19947814 | Increased awareness of the differences among incretin mimetics, GLP-1 analogs, and DPP-4 inhibitors, including their structures, half-lives, dosages, hemoglobin A(1c)-lowering capacities, effects on weight, and adverse events will help shape the future of these therapeutic agents. |
| 1085 | 19947817 | Incretin-based treatments, such as glucagon-like peptide-1 (GLP-1)-receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are the newest class of therapies for the management of patients with type 2 diabetes. |
| 1086 | 19952300 | Newer antidiabetes agents include incretin-based medications, such as the glucagon-like peptide-1 receptor agonists, which tend to decrease weight, and the dipeptidyl peptidase-4 inhibitors, which are weight neutral. |
| 1087 | 19952298 | Nutrient intake stimulates the secretion of the gastrointestinal incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which exert glucose-dependent insulinotropic effects and assist pancreatic insulin and glucagon in maintaining glucose homeostasis. |
| 1088 | 19952298 | An impaired incretin system, characterized by decreased responsiveness to GIP and markedly reduced GLP-1 concentration, occurs in individuals with type 2 diabetes mellitus (T2DM). |
| 1089 | 19952298 | The administration of GLP-1 improves glycemic control, but GLP-1 is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4). |
| 1090 | 19952298 | Exenatide, a DPP-4-resistant exendin-4 GLP-1 receptor agonist, exhibits the glucoregulatory actions of GLP-1 and reduces body weight in patients with T2DM. |
| 1091 | 19952298 | DPP-4 inhibitors such as sitagliptin and saxagliptin increase endogenous GLP-1 concentration and demonstrate incretin-associated glucoregulatory actions in patients with T2DM. |
| 1092 | 19952298 | Nutrient intake stimulates the secretion of the gastrointestinal incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which exert glucose-dependent insulinotropic effects and assist pancreatic insulin and glucagon in maintaining glucose homeostasis. |
| 1093 | 19952298 | An impaired incretin system, characterized by decreased responsiveness to GIP and markedly reduced GLP-1 concentration, occurs in individuals with type 2 diabetes mellitus (T2DM). |
| 1094 | 19952298 | The administration of GLP-1 improves glycemic control, but GLP-1 is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4). |
| 1095 | 19952298 | Exenatide, a DPP-4-resistant exendin-4 GLP-1 receptor agonist, exhibits the glucoregulatory actions of GLP-1 and reduces body weight in patients with T2DM. |
| 1096 | 19952298 | DPP-4 inhibitors such as sitagliptin and saxagliptin increase endogenous GLP-1 concentration and demonstrate incretin-associated glucoregulatory actions in patients with T2DM. |
| 1097 | 19952301 | Advances in therapy for type 2 diabetes: GLP-1 receptor agonists and DPP-4 inhibitors. |
| 1098 | 19952301 | This has led to the development of incretinbased therapies, such as glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. |
| 1099 | 19952301 | Advances in therapy for type 2 diabetes: GLP-1 receptor agonists and DPP-4 inhibitors. |
| 1100 | 19952301 | This has led to the development of incretinbased therapies, such as glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. |
| 1101 | 19952302 | Newer antidiabetes agents, such as the glucagon-like peptide-1 (GLP-1) receptor agonists and the dipeptidyl peptidase-4 (DPP-4) inhibitors, address fundamental defects related to glycemic control in T2DM and may have potential effects on other markers of cardiovascular risk. |
| 1102 | 19952303 | Antidiabetes agents targeting this system include dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. |
| 1103 | 20015035 | No single specific therapeutic agent can treat diabetic cardiomyopathy because once the disease is overt, the management may require a variety of approaches such as risk factors and lifestyle modification, glucose control (insulin, alpha glucosidase inhibitors, sulfonylureas, biguanides, meglitinides, thiazolidinediones and dipeptidyl peptidase 4 (DPP-4) inhibitors); hormones (IGF-1); ACE inhibitors (captopril, enalapril); angiotensin II receptor antagonists (losartan, olmesartan); beta adrenoreceptor antagonists (acebutolol, carvedilol); peptides (adrenomedullin); endothelin-1 receptor antagonists (bosentan, tezosentan); calcium channel blockers (amlodipine, verapamil); antioxidants (methalothionein, alpha tocopherol, alpha lipoic acid) and antihyperlipidemic drugs (simvastatin, fenofibrate, ezetimibe) to effectively treat patients with diabetic cardiomyopathy. |
| 1104 | 20043037 | Incretin-based analogues have been developed to extend endogenous GLP-1 action (GLP-1 receptor agonists) and to hamper its degradation (DPP-4 inhibitors). |
| 1105 | 20043037 | Evidence suggests that GLP-1 receptor agonists and DPP-4 inhibitors have different pharmacodynamic and pharmacokinetic effects. |
| 1106 | 20043037 | For example, GLP-1 receptor agonists deliver supraphysiologic levels of GLP-1 analogues designed to resist inactivation by DPP-4, whereas DPP-4 inhibition conserves native GLP-1 resulting in concentrations within the physiologic range. |
| 1107 | 20043037 | Furthermore, GLP-1 receptor agonists induce glucose-dependent insulin secretion, beta-cell protection, and other extraglycemic benefits such as weight loss and improvement in markers of cardiovascular risk. |
| 1108 | 20043037 | DPP-4 inhibition is dependent on the availability of endogenous GLP-1, which appears to be adversely affected by type 2 diabetes and its progression. |
| 1109 | 20043037 | Incretin-based analogues have been developed to extend endogenous GLP-1 action (GLP-1 receptor agonists) and to hamper its degradation (DPP-4 inhibitors). |
| 1110 | 20043037 | Evidence suggests that GLP-1 receptor agonists and DPP-4 inhibitors have different pharmacodynamic and pharmacokinetic effects. |
| 1111 | 20043037 | For example, GLP-1 receptor agonists deliver supraphysiologic levels of GLP-1 analogues designed to resist inactivation by DPP-4, whereas DPP-4 inhibition conserves native GLP-1 resulting in concentrations within the physiologic range. |
| 1112 | 20043037 | Furthermore, GLP-1 receptor agonists induce glucose-dependent insulin secretion, beta-cell protection, and other extraglycemic benefits such as weight loss and improvement in markers of cardiovascular risk. |
| 1113 | 20043037 | DPP-4 inhibition is dependent on the availability of endogenous GLP-1, which appears to be adversely affected by type 2 diabetes and its progression. |
| 1114 | 20043037 | Incretin-based analogues have been developed to extend endogenous GLP-1 action (GLP-1 receptor agonists) and to hamper its degradation (DPP-4 inhibitors). |
| 1115 | 20043037 | Evidence suggests that GLP-1 receptor agonists and DPP-4 inhibitors have different pharmacodynamic and pharmacokinetic effects. |
| 1116 | 20043037 | For example, GLP-1 receptor agonists deliver supraphysiologic levels of GLP-1 analogues designed to resist inactivation by DPP-4, whereas DPP-4 inhibition conserves native GLP-1 resulting in concentrations within the physiologic range. |
| 1117 | 20043037 | Furthermore, GLP-1 receptor agonists induce glucose-dependent insulin secretion, beta-cell protection, and other extraglycemic benefits such as weight loss and improvement in markers of cardiovascular risk. |
| 1118 | 20043037 | DPP-4 inhibition is dependent on the availability of endogenous GLP-1, which appears to be adversely affected by type 2 diabetes and its progression. |
| 1119 | 20043037 | Incretin-based analogues have been developed to extend endogenous GLP-1 action (GLP-1 receptor agonists) and to hamper its degradation (DPP-4 inhibitors). |
| 1120 | 20043037 | Evidence suggests that GLP-1 receptor agonists and DPP-4 inhibitors have different pharmacodynamic and pharmacokinetic effects. |
| 1121 | 20043037 | For example, GLP-1 receptor agonists deliver supraphysiologic levels of GLP-1 analogues designed to resist inactivation by DPP-4, whereas DPP-4 inhibition conserves native GLP-1 resulting in concentrations within the physiologic range. |
| 1122 | 20043037 | Furthermore, GLP-1 receptor agonists induce glucose-dependent insulin secretion, beta-cell protection, and other extraglycemic benefits such as weight loss and improvement in markers of cardiovascular risk. |
| 1123 | 20043037 | DPP-4 inhibition is dependent on the availability of endogenous GLP-1, which appears to be adversely affected by type 2 diabetes and its progression. |
| 1124 | 20082581 | The role of basal insulin and glucagon-like peptide-1 agonists in the therapeutic management of type 2 diabetes--a comprehensive review. |
| 1125 | 20082581 | The treatment of type 2 diabetes mellitus (T2DM) has been revolutionized by the introduction of novel therapeutic regimens following the clinical approval of the long-acting basal insulin glargine 10 years ago, followed by insulin detemir and, more recently, agents that target the glucagon-like peptide (GLP)-1 system with dipeptidyl peptidase 4 (DPP-4)-resistant products, such as liraglutide and exenatide, and DPP-4 inhibitors, such as sitagliptin, saxagliptin, alogliptin, and vildagliptin. |
| 1126 | 20082581 | The position and clinical efficacy of the GLP-1 mimetics are less well understood, however, and how they should be best used in the context of the established clinical efficacy of long-acting insulin analogs is yet to be defined. |
| 1127 | 20082581 | The aim of this review is to provide a summary of the efficacy, safety, and weight changes associated with long-acting insulin analogs (insulin glargine and insulin detemir) and two GLP-1 mimetics (exenatide and liraglutide). |
| 1128 | 20082581 | This literature review demonstrates that GLP-1 and basal insulin therapies are effective treatment options for insulin-naïve patients with suboptimal glycemic control with oral hypoglycemic agents. |
| 1129 | 20082581 | There are potential advantages of basal insulin and GLP-1 therapies in particular populations of patients. |
| 1130 | 20092903 | Lack of preservation of insulin gene expression by a glucagon-like peptide 1 agonist or a dipeptidyl peptidase 4 inhibitor in an in vivo model of glucolipotoxicity. |
| 1131 | 20107301 | Newer pharmacotherapies include the glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and amylinomimetics. |
| 1132 | 20115929 | The incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are secreted in the gut upon meal ingestion and lower blood glucose by glucose-dependent stimulation of insulin secretion and production. |
| 1133 | 20115929 | Thus, injectable DPP-4-resistant GLP-1 receptor agonists (GLP-1RA) and oral DPP-4 inhibitors have been developed. |
| 1134 | 20115930 | Available anti-diabetic oral drugs include insulin secretagogues (meglitinides and sulfonylureas), biguanides (metformin) alpha-glucosidase inhibitors, thiazolidinediones (TZDs) and newly introduced glucagon-like peptide-1 (GLP-1) analogues and inhibitors of GLP-1 degrading enzyme dipeptidyl peptidase-4 (DPP-4). |
| 1135 | 20130739 | Role of glucagon-like peptide-1 analogues on insulin receptor regulation in diabetic rat hearts. |
| 1136 | 20130739 | Male rats were divided into the following 9 groups: nondiabetic (N), nondiabetic treated with exendin-4 (NE), nondiabetic treated with dipeptidyl peptidase IV (DPP-IV) inhibitor (NDp), diabetic (D), diabetic treated with insulin (DI), diabetic treated with exendin-4 (DE), diabetic co-treated with insulin and exendin-4 (DIE), diabetic treated with DPP-IV inhibitor (DDp), and diabetic co-treated with insulin and DPP-IV inhibitor (DIDp). |
| 1137 | 20130739 | After the rats were treated for 1 month, a first-order Bessel function was employed to estimate the insulin binding affinity (with time constant tau = 1/k-n) to its receptors on the coronary endothelium and cardiomyocytes using CHAPS-untreated and CHAPS-treated heart perfusion, respectively. |
| 1138 | 20130739 | Treatment with insulin and (or) exendin-4, a glucagon-like peptide-1 (GLP-1) analogue, increased tau on the coronary endothelium only. |
| 1139 | 20130739 | Therefore, negative myocardial effects related to the insulin receptor were diminished in diabetic rats treated with DPP-IV inhibitor and, more efficiently, by exendin-4. |
| 1140 | 20130739 | Role of glucagon-like peptide-1 analogues on insulin receptor regulation in diabetic rat hearts. |
| 1141 | 20130739 | Male rats were divided into the following 9 groups: nondiabetic (N), nondiabetic treated with exendin-4 (NE), nondiabetic treated with dipeptidyl peptidase IV (DPP-IV) inhibitor (NDp), diabetic (D), diabetic treated with insulin (DI), diabetic treated with exendin-4 (DE), diabetic co-treated with insulin and exendin-4 (DIE), diabetic treated with DPP-IV inhibitor (DDp), and diabetic co-treated with insulin and DPP-IV inhibitor (DIDp). |
| 1142 | 20130739 | After the rats were treated for 1 month, a first-order Bessel function was employed to estimate the insulin binding affinity (with time constant tau = 1/k-n) to its receptors on the coronary endothelium and cardiomyocytes using CHAPS-untreated and CHAPS-treated heart perfusion, respectively. |
| 1143 | 20130739 | Treatment with insulin and (or) exendin-4, a glucagon-like peptide-1 (GLP-1) analogue, increased tau on the coronary endothelium only. |
| 1144 | 20130739 | Therefore, negative myocardial effects related to the insulin receptor were diminished in diabetic rats treated with DPP-IV inhibitor and, more efficiently, by exendin-4. |
| 1145 | 20130920 | These comprise the injectable GLP-1 receptor agonists solely acting on the GLP-1 receptor on the one hand and orally active dipeptidyl-peptidase inhibitors (DPP-4 inhibitors) raising endogenous GLP-1 and other hormone levels by inhibiting the degrading enzyme DPP-4. |
| 1146 | 20130920 | GLP-1 receptor agonists allow weight loss, whereas DPP-4 inhibitors are weight neutral. |
| 1147 | 20130920 | These comprise the injectable GLP-1 receptor agonists solely acting on the GLP-1 receptor on the one hand and orally active dipeptidyl-peptidase inhibitors (DPP-4 inhibitors) raising endogenous GLP-1 and other hormone levels by inhibiting the degrading enzyme DPP-4. |
| 1148 | 20130920 | GLP-1 receptor agonists allow weight loss, whereas DPP-4 inhibitors are weight neutral. |
| 1149 | 20136169 | The available oral antidiabetic drugs include insulin secretagogues (meglitinides and sulfonylureas), biguanides (metformin), alpha-glucosidase inhibitors, thiazolidinediones and newly introduced inhibitors of glucagon-like peptide 1 degrading enzyme dipeptidyl peptidase 4 (DPP-4). |
| 1150 | 20143560 | The following preparations are recommended to subjects with DM2 and PH: alpha-glucosidase inhibitors, glynides, ultrashort-acting insulin analogs, dipeptidylpeptidase-4 inhibitors, exenatide (incretin mimetic). |
| 1151 | 20152998 | The therapeutic potential of GLP-1 in diabetes is limited by rapid inactivation by the enzyme dipeptidylpeptidase-4 (DPP-4). |
| 1152 | 20152998 | Ten subjects with type 2 diabetes mellitus (8 male and 2 female; age, 68.7 ± 2.6 years [mean ± SEM]; body mass index, 29.6 ± 1.7 kg/m²; hemoglobin A(1c), 7.0% ± 0.1%) received 1 of 3 combinations after an overnight fast in a randomized crossover design: metformin 1 g orally plus subcutaneous injection saline (Metformin), GLP-1 (1.5 nmol/kg body weight subcutaneously) plus placebo tablet (GLP-1), or metformin 1 g plus GLP-1(Metformin + GLP-1). |
| 1153 | 20152998 | Mean AUC serum insulin responses were similar after either Metformin + GLP-1 (5426 ± 498 mU/[L min]) or GLP-1 (5655 ± 854 mU/[L min]) treatment, and both were higher than Metformin (3521 ± 410 mU/[L min]; P < .001 and P < .05, respectively). |
| 1154 | 20152998 | In combination with GLP-1, metformin significantly lowers plasma glucose concentrations in type 2 diabetes mellitus subjects compared with GLP-1 alone, whereas insulin responses were similar. |
| 1155 | 20198559 | Dipeptidyl-peptidase 4 and attractin expression is increased in circulating blood monocytes of obese human subjects. |
| 1156 | 20198559 | Dipeptidyl-peptidase (DPP)-4, which catalizes the degradation of the insulinotropic incretin glucagon-like-peptide (GLP)-1, and the DPP-4 like enzyme attractin are involved in activation of T-lymphocytes and monocytes. |
| 1157 | 20198559 | The aim of the present study was to examine the expression of DPP-4 and attractin in circulating blood monocytes of obese and type 2 diabetic subjects. |
| 1158 | 20198559 | DPP-4 and attractin were detectable in human circulating monocytes with attractin being expressed at higher levels compared to DPP-4. |
| 1159 | 20198559 | Finally, neither DPP-4 nor attractin expression was altered by sitagliptin or insulin treatment. |
| 1160 | 20198559 | In conclusion, our data demonstrate, that expressions of DPP-4 and attractin in circulating blood monocytes of human subjects are influenced by metabolic abnormalities with obesity being an important factor. |
| 1161 | 20198559 | Dipeptidyl-peptidase 4 and attractin expression is increased in circulating blood monocytes of obese human subjects. |
| 1162 | 20198559 | Dipeptidyl-peptidase (DPP)-4, which catalizes the degradation of the insulinotropic incretin glucagon-like-peptide (GLP)-1, and the DPP-4 like enzyme attractin are involved in activation of T-lymphocytes and monocytes. |
| 1163 | 20198559 | The aim of the present study was to examine the expression of DPP-4 and attractin in circulating blood monocytes of obese and type 2 diabetic subjects. |
| 1164 | 20198559 | DPP-4 and attractin were detectable in human circulating monocytes with attractin being expressed at higher levels compared to DPP-4. |
| 1165 | 20198559 | Finally, neither DPP-4 nor attractin expression was altered by sitagliptin or insulin treatment. |
| 1166 | 20198559 | In conclusion, our data demonstrate, that expressions of DPP-4 and attractin in circulating blood monocytes of human subjects are influenced by metabolic abnormalities with obesity being an important factor. |
| 1167 | 20198559 | Dipeptidyl-peptidase 4 and attractin expression is increased in circulating blood monocytes of obese human subjects. |
| 1168 | 20198559 | Dipeptidyl-peptidase (DPP)-4, which catalizes the degradation of the insulinotropic incretin glucagon-like-peptide (GLP)-1, and the DPP-4 like enzyme attractin are involved in activation of T-lymphocytes and monocytes. |
| 1169 | 20198559 | The aim of the present study was to examine the expression of DPP-4 and attractin in circulating blood monocytes of obese and type 2 diabetic subjects. |
| 1170 | 20198559 | DPP-4 and attractin were detectable in human circulating monocytes with attractin being expressed at higher levels compared to DPP-4. |
| 1171 | 20198559 | Finally, neither DPP-4 nor attractin expression was altered by sitagliptin or insulin treatment. |
| 1172 | 20198559 | In conclusion, our data demonstrate, that expressions of DPP-4 and attractin in circulating blood monocytes of human subjects are influenced by metabolic abnormalities with obesity being an important factor. |
| 1173 | 20198559 | Dipeptidyl-peptidase 4 and attractin expression is increased in circulating blood monocytes of obese human subjects. |
| 1174 | 20198559 | Dipeptidyl-peptidase (DPP)-4, which catalizes the degradation of the insulinotropic incretin glucagon-like-peptide (GLP)-1, and the DPP-4 like enzyme attractin are involved in activation of T-lymphocytes and monocytes. |
| 1175 | 20198559 | The aim of the present study was to examine the expression of DPP-4 and attractin in circulating blood monocytes of obese and type 2 diabetic subjects. |
| 1176 | 20198559 | DPP-4 and attractin were detectable in human circulating monocytes with attractin being expressed at higher levels compared to DPP-4. |
| 1177 | 20198559 | Finally, neither DPP-4 nor attractin expression was altered by sitagliptin or insulin treatment. |
| 1178 | 20198559 | In conclusion, our data demonstrate, that expressions of DPP-4 and attractin in circulating blood monocytes of human subjects are influenced by metabolic abnormalities with obesity being an important factor. |
| 1179 | 20198559 | Dipeptidyl-peptidase 4 and attractin expression is increased in circulating blood monocytes of obese human subjects. |
| 1180 | 20198559 | Dipeptidyl-peptidase (DPP)-4, which catalizes the degradation of the insulinotropic incretin glucagon-like-peptide (GLP)-1, and the DPP-4 like enzyme attractin are involved in activation of T-lymphocytes and monocytes. |
| 1181 | 20198559 | The aim of the present study was to examine the expression of DPP-4 and attractin in circulating blood monocytes of obese and type 2 diabetic subjects. |
| 1182 | 20198559 | DPP-4 and attractin were detectable in human circulating monocytes with attractin being expressed at higher levels compared to DPP-4. |
| 1183 | 20198559 | Finally, neither DPP-4 nor attractin expression was altered by sitagliptin or insulin treatment. |
| 1184 | 20198559 | In conclusion, our data demonstrate, that expressions of DPP-4 and attractin in circulating blood monocytes of human subjects are influenced by metabolic abnormalities with obesity being an important factor. |
| 1185 | 20198559 | Dipeptidyl-peptidase 4 and attractin expression is increased in circulating blood monocytes of obese human subjects. |
| 1186 | 20198559 | Dipeptidyl-peptidase (DPP)-4, which catalizes the degradation of the insulinotropic incretin glucagon-like-peptide (GLP)-1, and the DPP-4 like enzyme attractin are involved in activation of T-lymphocytes and monocytes. |
| 1187 | 20198559 | The aim of the present study was to examine the expression of DPP-4 and attractin in circulating blood monocytes of obese and type 2 diabetic subjects. |
| 1188 | 20198559 | DPP-4 and attractin were detectable in human circulating monocytes with attractin being expressed at higher levels compared to DPP-4. |
| 1189 | 20198559 | Finally, neither DPP-4 nor attractin expression was altered by sitagliptin or insulin treatment. |
| 1190 | 20198559 | In conclusion, our data demonstrate, that expressions of DPP-4 and attractin in circulating blood monocytes of human subjects are influenced by metabolic abnormalities with obesity being an important factor. |
| 1191 | 20206729 | Glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, secreted from the L-cells of the lower gut and K-cells of the intestines, respectively, are responsible for these incretin effects, which are reduced in patients with type 2 diabetes mellitus. |
| 1192 | 20206729 | Sitagliptin inhibits the DPP-4 enzyme, thus increasing the half-life of endogenous GLP-1. |
| 1193 | 20206729 | This review examines data from recent GLP-1 receptor agonist and DPP-4 inhibitor studies in patients with type 2 diabetes, as well as data on other incretin-based therapies in clinical development. |
| 1194 | 20206729 | Glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, secreted from the L-cells of the lower gut and K-cells of the intestines, respectively, are responsible for these incretin effects, which are reduced in patients with type 2 diabetes mellitus. |
| 1195 | 20206729 | Sitagliptin inhibits the DPP-4 enzyme, thus increasing the half-life of endogenous GLP-1. |
| 1196 | 20206729 | This review examines data from recent GLP-1 receptor agonist and DPP-4 inhibitor studies in patients with type 2 diabetes, as well as data on other incretin-based therapies in clinical development. |
| 1197 | 20217513 | The long-term improvement was demonstrated with short-term intensive insulin therapy of newly diagnosed DM2, the use of antiapoptotic drugs such as glitazones, and the use of glucagon-like peptide-1 receptor agonists (GLP-1 mimetics), not inactivated by the enzyme dipeptidyl peptidase 4 and/or to inhibit that enzyme (GLP-1 enhancers). |
| 1198 | 20217513 | From the two major incretins, GLP-1 and GIP (glucose-dependent insulinotropic polypeptide), only the first one or its mimetics or enhancers can be used for treatment. |
| 1199 | 20336594 | DPP-4 quickly degrades the insulin secretory hormones, glucose-dependent insulinotropic peptide and glucagon-like peptide-1; thus inhibiting the degradation of these hormones is a viable treatment option for patients with T2DM. |
| 1200 | 20374254 | Because DPPIV inhibitors are often used in metabolic syndrome, it is important to determine whether DPPIV inhibition in this setting enhances renovascular responses to AngII. 2. |
| 1201 | 20382837 | Incretin-based therapies developed to treat patients with T2DM, including oral dipeptidyl peptidase-4 inhibitor agents or glucagon-like peptide-1 agonists, offer the potential of sustained glycemic control for many patients without the adverse events associated with other classes of antihyperglycemic medications. |
| 1202 | 20382839 | Two classes of incretin-directed therapies are available and work by either increasing endogenous levels of glucagon-like peptide-1 (GLP-1) (ie, dipeptidyl peptidase-4 inhibitors) or by mimicking the activity of endogenous GLP-1 (ie, GLP-1 agonists). |
| 1203 | 20384864 | About CD26 CD8 lymphocytes in type 1 diabetes mellitus. |
| 1204 | 20431808 | These 50 functional genes are responsible for diabetic nephropathy; of these 50, some of the genes which are more expressed and responsible are AGXT: Alanine-glyoxylate aminotransferase, RHOD: Ras homolog gene family, CAPN6: Calpain 6, EFNB2: Ephrin-B2, ANXA7: Annexin A7, PEG10: Paternally expressed 10, DPP4: Dipeptidyl-peptidase 4 (CD26, adenosine deaminase complexing protein 2), ENSA: Endosulfine alpha, IGFBP2: Insulin-like growth factor binding protein 2, 36kDa, CENPB: Centromere protein B, 80kDa, MLL3: Myeloid/lymphoid or mixed-lineage leukemia 3, BDNF: Brain-derived neurotrophic factor, EIF4A2: Eukaryotic translation initiation factor 4A, isoform 2, PPP2R1A: Protein phosphatase 2 (formerly 2A), regulatory subunit A, alpha isoform. |
| 1205 | 20444936 | Inhibition of dipeptidyl peptidase IV (DPP-IV) activity by NVP-DPP728, a DPP-IV inhibitor, improves the therapeutic efficacy of glucagon-like peptide-1 (GLP-1). |
| 1206 | 20444936 | Regulatory T cells in thymus and secondary lymph nodes, TGF-beta1 and GLP-1 in plasma, and the insulin content in the pancreas were measured. |
| 1207 | 20444936 | Insulitis was reduced and the percentage of CD4(+)CD25(+)FoxP3(+) regulatory T cells was increased in treated NOD mice with remission. |
| 1208 | 20444936 | Plasma TGF-beta1 and GLP-1, the insulin content, and both insulin(+) and BrdU(+) beta-cells in pancreas were also significantly increased. |
| 1209 | 20444936 | In conclusion, NVP-DPP728 treatment can reverse new-onset diabetes in NOD mice by reducing insulitis, increasing CD4(+)CD25(+)FoxP3(+) regulatory T cells, and stimulating beta-cell replication. beta-Cell replication is not associated with the degree of inflammation in NVP-DPP728-treated NOD mice. |
| 1210 | 20448799 | Treatment options, including the new dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 mimetics that primarily target postprandial hyperglycemia, are also discussed. |
| 1211 | 20455069 | GLP-1 is rapidly inactivated in vivo, mainly by the DPP-4. |
| 1212 | 20455069 | Some authors suggest that Metformin has no direct inhibitory effect on DPP-4 activity and that Metformin and the other biguanides enhance GLP-1 secretion; others suggest a possible role of Metformin in the inhibition of the DPP-4 activity. |
| 1213 | 20455069 | In order to better elucidate the role of insulin sensitizers on the modulation of GLP-1 circulating levels, DPP-4 activity and mRNA expression were measured in cultured human aortic endothelial cells (HAEC) and human microvascular dermal endothelial cells (HMVEC) exposed to high glucose, Metformin and Rosiglitazone. |
| 1214 | 20455069 | GLP-1 is rapidly inactivated in vivo, mainly by the DPP-4. |
| 1215 | 20455069 | Some authors suggest that Metformin has no direct inhibitory effect on DPP-4 activity and that Metformin and the other biguanides enhance GLP-1 secretion; others suggest a possible role of Metformin in the inhibition of the DPP-4 activity. |
| 1216 | 20455069 | In order to better elucidate the role of insulin sensitizers on the modulation of GLP-1 circulating levels, DPP-4 activity and mRNA expression were measured in cultured human aortic endothelial cells (HAEC) and human microvascular dermal endothelial cells (HMVEC) exposed to high glucose, Metformin and Rosiglitazone. |
| 1217 | 20455069 | GLP-1 is rapidly inactivated in vivo, mainly by the DPP-4. |
| 1218 | 20455069 | Some authors suggest that Metformin has no direct inhibitory effect on DPP-4 activity and that Metformin and the other biguanides enhance GLP-1 secretion; others suggest a possible role of Metformin in the inhibition of the DPP-4 activity. |
| 1219 | 20455069 | In order to better elucidate the role of insulin sensitizers on the modulation of GLP-1 circulating levels, DPP-4 activity and mRNA expression were measured in cultured human aortic endothelial cells (HAEC) and human microvascular dermal endothelial cells (HMVEC) exposed to high glucose, Metformin and Rosiglitazone. |
| 1220 | 20463416 | By enhancing and prolonging incretin effects, DPP-4 inhibitors stimulate glucose-dependent insulin secretion and also reduce glucagon secretion. |
| 1221 | 20463424 | Incretin-based therapies, including glucagon-like peptide-1 (GLP-1) receptor agonists, mimic the effects of native GLP-1, while dipeptidyl peptidase-4 inhibitors increase circulating concentrations of endogenous GLP-1. |
| 1222 | 20500049 | Incretin-based therapies encompass two new classes of antidiabetic drugs: glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide, exenatide, and exenatide long-acting release), which are structurally related to GLP-1, and the dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin and saxagliptin), which limit the breakdown of endogenous GLP-1. |
| 1223 | 20500049 | Data show that these therapies affect insulin secretion in a glucose-dependent manner, achieving clinically meaningful reductions in hemoglobin A(1c) levels, with very low rates of hypoglycemia. |
| 1224 | 20518191 | Available anti-diabetic oral drugs include insulin secretagogues (meglitinides and sulfonylureas), biguanides (metformin), alpha-glucosidase inhibitors, thiazolidinediones (TZDs) and newly introduced glucagon-like peptide-1 (GLP-1) analogues and inhibitors of GLP-1 degrading enzyme dipeptidyl peptidase-4 (DPP-4). |
| 1225 | 20518803 | New classes of glucose-lowering agents have expanded the treatment options available to clinicians and patients and include the dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. |
| 1226 | 20519242 | New intravenous or oral agents include the incretin glucagon-like peptide 1 (GLP1), its analogues, and dipeptidyl peptidase-4 inhibitors, which potentiate the activity of GLP1 and thus enhance glucose-dependent insulin secretion. |
| 1227 | 20519806 | alpha-glucosidase inhibitors (alphaGIs) increase active glucagon-like peptide-1 (GLP-1) and reduce the total glucosedependent insulinotropic polypeptide (GIP) levels, but their ability to prevent diabetes remains uncertain. |
| 1228 | 20519806 | Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as sitagliptin, increase active GLP-1 and GIP levels and improve hyperglycemia in a glucose-dependent fashion. |
| 1229 | 20525907 | Incretin-based compounds, including glucagon-like peptide-1 receptor agonists and dipeptidyl-peptidase-4 inhibitors, have emerged as a new class of agents for the treatment of type 2 diabetes. |
| 1230 | 20526441 | Saxagliptin, a potent, selective dipeptidyl peptidase-4 (DPP-4) inhibitor specifically designed for extended inhibition of the DPP-4 enzyme, causes increased endogenous GLP-1 concentration. |
| 1231 | 20526441 | Saxagliptin provided significant reductions in hemoglobin HbA(1c) when given with metformin, glyburide, a TZD, or as monotherapy. |
| 1232 | 20539105 | Dipeptidyl peptidase-4 enzyme inhibitors are novel drugs that prolong the action of incretins, and lead to increased insulin secretion and reduced hepatic glucose production. |
| 1233 | 20575217 | Two drug classes-namely, the injectable glucagon-like peptide 1 (GLP-1) receptor agonists, which produce pharmacological GLP receptor activity, and the oral dipeptidyl peptidase-4 (DPP-4) inhibitors, which raise levels of endogenously produced GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) by preventing enzymatic degradation--have been available for several years. |
| 1234 | 20676118 | Two approaches have been adopted: GLP-1 receptor agonists that mimic the effects of native GLP-1 and dipeptidyl peptidase-4 inhibitors that increase endogenous GLP-1 levels. |
| 1235 | 20687610 | However, its rapid degradation by enzymes like dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) 24.11 severely compromises its effective clinical use. |
| 1236 | 20687610 | Whereas specific DPP-IV inhibitors have been developed, NEP 24.11 targets multiple sites in the GLP-1 sequence, which makes it difficult to block. |
| 1237 | 20687610 | These highly constrained peptides are the first examples of NEP 24.11-resistant GLP-1 analogues. |
| 1238 | 20687610 | However, its rapid degradation by enzymes like dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) 24.11 severely compromises its effective clinical use. |
| 1239 | 20687610 | Whereas specific DPP-IV inhibitors have been developed, NEP 24.11 targets multiple sites in the GLP-1 sequence, which makes it difficult to block. |
| 1240 | 20687610 | These highly constrained peptides are the first examples of NEP 24.11-resistant GLP-1 analogues. |
| 1241 | 20708812 | Since the launch of sitagliptin in 2006, a compelling body of evidence has accumulated showing that dipeptidyl peptidase-4 (DPP-4) inhibitors, which augment endogenous GLP-1 and GIP levels, represent an important advance in the management of T2DM. |
| 1242 | 20736387 | The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are now known to play major roles in endogenous glucose control, including regulation of insulin, glucagon, and hepatic glucose metabolism. |
| 1243 | 20736387 | Investigation of the incretin system has led to development of drugs that mimic or enhance the endogenous hormones, including GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. |
| 1244 | 20805868 | Serum dipeptidyl peptidase-4 activity in insulin resistant patients with non-alcoholic fatty liver disease: a novel liver disease biomarker. |
| 1245 | 20809667 | Of the incretin-based therapies, both the dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon-like peptide-1 (GLP-1) receptor agonists stimulate insulin secretion and inhibit glucagon secretion. |
| 1246 | 20809667 | The subsequent review outlines evidence from selected clinical trials of the currently available GLP-1 receptor agonists, exenatide and liraglutide, and DPP-4 inhibitors, sitagliptin and saxagliptin. |
| 1247 | 20809667 | Of the incretin-based therapies, both the dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon-like peptide-1 (GLP-1) receptor agonists stimulate insulin secretion and inhibit glucagon secretion. |
| 1248 | 20809667 | The subsequent review outlines evidence from selected clinical trials of the currently available GLP-1 receptor agonists, exenatide and liraglutide, and DPP-4 inhibitors, sitagliptin and saxagliptin. |
| 1249 | 20824238 | The "treat to target" approach is to quickly achieve the target glycosylated hemoglobin (AIC) goal of <7% in most people, and then intensify or change therapy as needed to maintain glycemic control. |
| 1250 | 20824238 | The increasingly important roles of the GLP-1 agonists and DPP-4 inhibitors stem from their overall good efficacy and safety profiles compared with other treatment options. |
| 1251 | 20831513 | Incretin based therapy is one of several newer therapies to improve glycaemia and is available in two different forms, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists. |
| 1252 | 20831513 | DPP-4 inhibitors are oral drugs which are weight neutral, while GLP-1 agonists are injected subcutaneously and help promote weight loss while improving glycaemia. |
| 1253 | 20831513 | Other therapies in development for the treatment of T2DM include sodium-glucose transporter 2 (SGLT-2) inhibitors, glucagon receptor antagonists, glucokinase activators and sirtuins. |
| 1254 | 20831513 | Incretin based therapy is one of several newer therapies to improve glycaemia and is available in two different forms, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists. |
| 1255 | 20831513 | DPP-4 inhibitors are oral drugs which are weight neutral, while GLP-1 agonists are injected subcutaneously and help promote weight loss while improving glycaemia. |
| 1256 | 20831513 | Other therapies in development for the treatment of T2DM include sodium-glucose transporter 2 (SGLT-2) inhibitors, glucagon receptor antagonists, glucokinase activators and sirtuins. |
| 1257 | 20852989 | GLP-1 signaling preserves cardiac function in endotoxemic Fischer 344 and DPP4-deficient rats. |
| 1258 | 20852989 | Glucagon-like peptide-1 (GLP-1) is rapidly cleaved by widely expressed dipeptidyl peptidase-4 (DPP4) enzyme. |
| 1259 | 20852989 | Both DPP4 inhibitors and GLP-1 analogue are being developed as a novel class of oral antihyperglycemic agent in the treatment of diabetes. |
| 1260 | 20852989 | DPP4-deficient rats had better preservation of cardiovascular function than wild-type rats during endotoxemia, which was correlated with a more prominent elevation of GLP-1 signaling. |
| 1261 | 20852989 | Furthermore, the benefit of DPP4 deficiency or GLP-1 analogue not only preserved cardiovascular function but also alleviated multiple organ injury and improved survival rate during endotoxemia. |
| 1262 | 20852989 | In summary, this study demonstrated that the resistance to LPS in DPP4-deficient rats seems to be derived from the higher GLP-1 production, and exendin-4 prevents cardiac dysfunction in wild-type rats with endotoxemia. |
| 1263 | 20852989 | This study proves that GLP-1 agonists or DPP4 inhibitor may possibly be used as a preventive or even as a novel therapeutic agent in septic shock. |
| 1264 | 20852989 | GLP-1 signaling preserves cardiac function in endotoxemic Fischer 344 and DPP4-deficient rats. |
| 1265 | 20852989 | Glucagon-like peptide-1 (GLP-1) is rapidly cleaved by widely expressed dipeptidyl peptidase-4 (DPP4) enzyme. |
| 1266 | 20852989 | Both DPP4 inhibitors and GLP-1 analogue are being developed as a novel class of oral antihyperglycemic agent in the treatment of diabetes. |
| 1267 | 20852989 | DPP4-deficient rats had better preservation of cardiovascular function than wild-type rats during endotoxemia, which was correlated with a more prominent elevation of GLP-1 signaling. |
| 1268 | 20852989 | Furthermore, the benefit of DPP4 deficiency or GLP-1 analogue not only preserved cardiovascular function but also alleviated multiple organ injury and improved survival rate during endotoxemia. |
| 1269 | 20852989 | In summary, this study demonstrated that the resistance to LPS in DPP4-deficient rats seems to be derived from the higher GLP-1 production, and exendin-4 prevents cardiac dysfunction in wild-type rats with endotoxemia. |
| 1270 | 20852989 | This study proves that GLP-1 agonists or DPP4 inhibitor may possibly be used as a preventive or even as a novel therapeutic agent in septic shock. |
| 1271 | 20852989 | GLP-1 signaling preserves cardiac function in endotoxemic Fischer 344 and DPP4-deficient rats. |
| 1272 | 20852989 | Glucagon-like peptide-1 (GLP-1) is rapidly cleaved by widely expressed dipeptidyl peptidase-4 (DPP4) enzyme. |
| 1273 | 20852989 | Both DPP4 inhibitors and GLP-1 analogue are being developed as a novel class of oral antihyperglycemic agent in the treatment of diabetes. |
| 1274 | 20852989 | DPP4-deficient rats had better preservation of cardiovascular function than wild-type rats during endotoxemia, which was correlated with a more prominent elevation of GLP-1 signaling. |
| 1275 | 20852989 | Furthermore, the benefit of DPP4 deficiency or GLP-1 analogue not only preserved cardiovascular function but also alleviated multiple organ injury and improved survival rate during endotoxemia. |
| 1276 | 20852989 | In summary, this study demonstrated that the resistance to LPS in DPP4-deficient rats seems to be derived from the higher GLP-1 production, and exendin-4 prevents cardiac dysfunction in wild-type rats with endotoxemia. |
| 1277 | 20852989 | This study proves that GLP-1 agonists or DPP4 inhibitor may possibly be used as a preventive or even as a novel therapeutic agent in septic shock. |
| 1278 | 20852989 | GLP-1 signaling preserves cardiac function in endotoxemic Fischer 344 and DPP4-deficient rats. |
| 1279 | 20852989 | Glucagon-like peptide-1 (GLP-1) is rapidly cleaved by widely expressed dipeptidyl peptidase-4 (DPP4) enzyme. |
| 1280 | 20852989 | Both DPP4 inhibitors and GLP-1 analogue are being developed as a novel class of oral antihyperglycemic agent in the treatment of diabetes. |
| 1281 | 20852989 | DPP4-deficient rats had better preservation of cardiovascular function than wild-type rats during endotoxemia, which was correlated with a more prominent elevation of GLP-1 signaling. |
| 1282 | 20852989 | Furthermore, the benefit of DPP4 deficiency or GLP-1 analogue not only preserved cardiovascular function but also alleviated multiple organ injury and improved survival rate during endotoxemia. |
| 1283 | 20852989 | In summary, this study demonstrated that the resistance to LPS in DPP4-deficient rats seems to be derived from the higher GLP-1 production, and exendin-4 prevents cardiac dysfunction in wild-type rats with endotoxemia. |
| 1284 | 20852989 | This study proves that GLP-1 agonists or DPP4 inhibitor may possibly be used as a preventive or even as a novel therapeutic agent in septic shock. |
| 1285 | 20852989 | GLP-1 signaling preserves cardiac function in endotoxemic Fischer 344 and DPP4-deficient rats. |
| 1286 | 20852989 | Glucagon-like peptide-1 (GLP-1) is rapidly cleaved by widely expressed dipeptidyl peptidase-4 (DPP4) enzyme. |
| 1287 | 20852989 | Both DPP4 inhibitors and GLP-1 analogue are being developed as a novel class of oral antihyperglycemic agent in the treatment of diabetes. |
| 1288 | 20852989 | DPP4-deficient rats had better preservation of cardiovascular function than wild-type rats during endotoxemia, which was correlated with a more prominent elevation of GLP-1 signaling. |
| 1289 | 20852989 | Furthermore, the benefit of DPP4 deficiency or GLP-1 analogue not only preserved cardiovascular function but also alleviated multiple organ injury and improved survival rate during endotoxemia. |
| 1290 | 20852989 | In summary, this study demonstrated that the resistance to LPS in DPP4-deficient rats seems to be derived from the higher GLP-1 production, and exendin-4 prevents cardiac dysfunction in wild-type rats with endotoxemia. |
| 1291 | 20852989 | This study proves that GLP-1 agonists or DPP4 inhibitor may possibly be used as a preventive or even as a novel therapeutic agent in septic shock. |
| 1292 | 20852989 | GLP-1 signaling preserves cardiac function in endotoxemic Fischer 344 and DPP4-deficient rats. |
| 1293 | 20852989 | Glucagon-like peptide-1 (GLP-1) is rapidly cleaved by widely expressed dipeptidyl peptidase-4 (DPP4) enzyme. |
| 1294 | 20852989 | Both DPP4 inhibitors and GLP-1 analogue are being developed as a novel class of oral antihyperglycemic agent in the treatment of diabetes. |
| 1295 | 20852989 | DPP4-deficient rats had better preservation of cardiovascular function than wild-type rats during endotoxemia, which was correlated with a more prominent elevation of GLP-1 signaling. |
| 1296 | 20852989 | Furthermore, the benefit of DPP4 deficiency or GLP-1 analogue not only preserved cardiovascular function but also alleviated multiple organ injury and improved survival rate during endotoxemia. |
| 1297 | 20852989 | In summary, this study demonstrated that the resistance to LPS in DPP4-deficient rats seems to be derived from the higher GLP-1 production, and exendin-4 prevents cardiac dysfunction in wild-type rats with endotoxemia. |
| 1298 | 20852989 | This study proves that GLP-1 agonists or DPP4 inhibitor may possibly be used as a preventive or even as a novel therapeutic agent in septic shock. |
| 1299 | 20852989 | GLP-1 signaling preserves cardiac function in endotoxemic Fischer 344 and DPP4-deficient rats. |
| 1300 | 20852989 | Glucagon-like peptide-1 (GLP-1) is rapidly cleaved by widely expressed dipeptidyl peptidase-4 (DPP4) enzyme. |
| 1301 | 20852989 | Both DPP4 inhibitors and GLP-1 analogue are being developed as a novel class of oral antihyperglycemic agent in the treatment of diabetes. |
| 1302 | 20852989 | DPP4-deficient rats had better preservation of cardiovascular function than wild-type rats during endotoxemia, which was correlated with a more prominent elevation of GLP-1 signaling. |
| 1303 | 20852989 | Furthermore, the benefit of DPP4 deficiency or GLP-1 analogue not only preserved cardiovascular function but also alleviated multiple organ injury and improved survival rate during endotoxemia. |
| 1304 | 20852989 | In summary, this study demonstrated that the resistance to LPS in DPP4-deficient rats seems to be derived from the higher GLP-1 production, and exendin-4 prevents cardiac dysfunction in wild-type rats with endotoxemia. |
| 1305 | 20852989 | This study proves that GLP-1 agonists or DPP4 inhibitor may possibly be used as a preventive or even as a novel therapeutic agent in septic shock. |
| 1306 | 20857706 | Liraglutide (Victoza) is a peptide produced by DNA recombinant technology, which presents 97% homology with human glucagon-like peptide-1 (GLP-1) but is resistant to dipeptidylpeptidase-4, the enzyme that degrades the natural hormone. |
| 1307 | 20859539 | Glucagon-like peptide-1 deficiency/resistance contributes to islet cell dysfunction by impairing insulin secretion and increasing glucagon secretion. |
| 1308 | 20859539 | Dipeptidyl peptidase-4 (DPP-4) inhibitors improve pancreatic islet function by augmenting glucose-dependent insulin secretion and decreasing elevated plasma glucagon levels. |
| 1309 | 20859539 | Alogliptin is a new DPP-4 inhibitor that reduces glycosylated hemoglobin (HbA(1c)), is weight neutral, has an excellent safety profile, and can be used in combination with oral agents and insulin. |
| 1310 | 20859539 | Glucagon-like peptide-1 deficiency/resistance contributes to islet cell dysfunction by impairing insulin secretion and increasing glucagon secretion. |
| 1311 | 20859539 | Dipeptidyl peptidase-4 (DPP-4) inhibitors improve pancreatic islet function by augmenting glucose-dependent insulin secretion and decreasing elevated plasma glucagon levels. |
| 1312 | 20859539 | Alogliptin is a new DPP-4 inhibitor that reduces glycosylated hemoglobin (HbA(1c)), is weight neutral, has an excellent safety profile, and can be used in combination with oral agents and insulin. |
| 1313 | 20871975 | The incretin hormones gastric inhibitory polypeptide and especially glucagon-like peptide (GLP) have an important physiological function in augmenting postprandial insulin secretion. |
| 1314 | 20871975 | Such a deficiency is the rationale for replacing endogenous incretins with GLP-1 receptor agonists or re-normalising active GLP-1 concentrations with dipeptidyl peptidase-4 inhibitors. |
| 1315 | 20879969 | These can mainly be categorized into two broad classes; GLP-1 agonists/analogs (exenatide, liraglutide), and dipeptidyl peptidase- 4 inhibitors (sitagliptin, vildagliptin). |
| 1316 | 20883052 | Thiazolidinediones are insulin sensitizers developed specifically for T2DM, which act via activation of peroxisome proliferator-activated receptors (PPARs). |
| 1317 | 20883052 | Glycosylated haemoglobin, fasting glucose, insulin parameters and β-cell function are all improved with pioglitazone treatment, with efficacy similar to third-generation sulfonylureas, metformin and dipeptidyl peptidase-4 inhibitors. |
| 1318 | 20885921 | Dipeptidyl-peptidase-4 inhibitors are weight neutral, whereas glucagon-like peptide-1 analogs are associated with weight loss. |
| 1319 | 20936101 | These medications include insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs), meglitinides, α-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4) inhibitors. |
| 1320 | 20949698 | As native human GLP-1 has a half life of only approximately 2 min, researchers have developed molecules that act as GLP-1 receptor agonists or inhibit the enzyme responsible for GLP-1 degradation (dipeptidyl peptidase-4). |
| 1321 | 21075654 | From a clinical and fundamental point of view, it was concluded that, at the onset of diabetes, an initial triggering of GLP-1 secretion-by metformin coupled with a DPP4 inhibitor-would help to activate the gut-peripheral axis and, hence, restore adequate regulation of glycaemia. |
| 1322 | 21075654 | GLP-1 analogues would certainly be helpful in association with long-acting insulin (albeit off-label) in patients with impaired beta cells and GLP-1 secretory potential. |
| 1323 | 21094909 | This chapter focuses on the incretin hormones, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), and their therapeutic potential in treating patients with type 2 diabetes. |
| 1324 | 21094909 | Therefore, the actions of GLP-1 and GIP, which include potentiation of meal-induced insulin secretion and trophic effects on the beta-cell, have attracted a lot of interest. |
| 1325 | 21094909 | Two new drug classes based on the actions of the incretin hormones have been approved for therapy of type 2 diabetes: injectable long-acting stable analogs of GLP-1, incretin mimetics, and orally available inhibitors of dipeptidyl peptidase 4 (DPP4; the enzyme responsible for the rapid degradation of GLP-1 and GIP), the so-called incretin enhancers. |
| 1326 | 21106864 | Newer incretin-based therapies, such as glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors, which appear to have a favorable cardiovascular safety profile as well as the mechanistic possibility for a favorable cardiovascular risk impact, are suitable for earlier inclusion as part of combination regimens aimed at achieving comprehensive treatment success in patients with type 2 DM. |
| 1327 | 21106865 | Incorporating incretin-based therapies into clinical practice: differences between glucagon-like Peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors. |
| 1328 | 21106865 | Incretin dysfunction can be treated with glucagon-like peptide 1 (GLP-1) receptor agonists (eg, exenatide and liraglutide) or inhibitors of dipeptidyl peptidase 4 (DPP-4) (eg, sitagliptin and saxagliptin), the enzyme that degrades GLP-1. |
| 1329 | 21106865 | The GLP-1 receptor agonists and DPP-4 inhibitors both elevate GLP-1 activity and substantially improve glycemic control. |
| 1330 | 21106865 | The GLP-1 receptor agonists are more effective in lowering blood glucose and result in substantial weight loss, whereas therapy with DPP-4 inhibitors lowers blood glucose levels to a lesser degree, and they are weight neutral. |
| 1331 | 21106865 | In addition, unlike insulin or sulfonylureas, treatment with a GLP-1 receptor agonist or a DPP-4 inhibitor has not been associated with substantial hypoglycemia. |
| 1332 | 21106865 | Incorporating incretin-based therapies into clinical practice: differences between glucagon-like Peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors. |
| 1333 | 21106865 | Incretin dysfunction can be treated with glucagon-like peptide 1 (GLP-1) receptor agonists (eg, exenatide and liraglutide) or inhibitors of dipeptidyl peptidase 4 (DPP-4) (eg, sitagliptin and saxagliptin), the enzyme that degrades GLP-1. |
| 1334 | 21106865 | The GLP-1 receptor agonists and DPP-4 inhibitors both elevate GLP-1 activity and substantially improve glycemic control. |
| 1335 | 21106865 | The GLP-1 receptor agonists are more effective in lowering blood glucose and result in substantial weight loss, whereas therapy with DPP-4 inhibitors lowers blood glucose levels to a lesser degree, and they are weight neutral. |
| 1336 | 21106865 | In addition, unlike insulin or sulfonylureas, treatment with a GLP-1 receptor agonist or a DPP-4 inhibitor has not been associated with substantial hypoglycemia. |
| 1337 | 21106865 | Incorporating incretin-based therapies into clinical practice: differences between glucagon-like Peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors. |
| 1338 | 21106865 | Incretin dysfunction can be treated with glucagon-like peptide 1 (GLP-1) receptor agonists (eg, exenatide and liraglutide) or inhibitors of dipeptidyl peptidase 4 (DPP-4) (eg, sitagliptin and saxagliptin), the enzyme that degrades GLP-1. |
| 1339 | 21106865 | The GLP-1 receptor agonists and DPP-4 inhibitors both elevate GLP-1 activity and substantially improve glycemic control. |
| 1340 | 21106865 | The GLP-1 receptor agonists are more effective in lowering blood glucose and result in substantial weight loss, whereas therapy with DPP-4 inhibitors lowers blood glucose levels to a lesser degree, and they are weight neutral. |
| 1341 | 21106865 | In addition, unlike insulin or sulfonylureas, treatment with a GLP-1 receptor agonist or a DPP-4 inhibitor has not been associated with substantial hypoglycemia. |
| 1342 | 21106865 | Incorporating incretin-based therapies into clinical practice: differences between glucagon-like Peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors. |
| 1343 | 21106865 | Incretin dysfunction can be treated with glucagon-like peptide 1 (GLP-1) receptor agonists (eg, exenatide and liraglutide) or inhibitors of dipeptidyl peptidase 4 (DPP-4) (eg, sitagliptin and saxagliptin), the enzyme that degrades GLP-1. |
| 1344 | 21106865 | The GLP-1 receptor agonists and DPP-4 inhibitors both elevate GLP-1 activity and substantially improve glycemic control. |
| 1345 | 21106865 | The GLP-1 receptor agonists are more effective in lowering blood glucose and result in substantial weight loss, whereas therapy with DPP-4 inhibitors lowers blood glucose levels to a lesser degree, and they are weight neutral. |
| 1346 | 21106865 | In addition, unlike insulin or sulfonylureas, treatment with a GLP-1 receptor agonist or a DPP-4 inhibitor has not been associated with substantial hypoglycemia. |
| 1347 | 21106865 | Incorporating incretin-based therapies into clinical practice: differences between glucagon-like Peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors. |
| 1348 | 21106865 | Incretin dysfunction can be treated with glucagon-like peptide 1 (GLP-1) receptor agonists (eg, exenatide and liraglutide) or inhibitors of dipeptidyl peptidase 4 (DPP-4) (eg, sitagliptin and saxagliptin), the enzyme that degrades GLP-1. |
| 1349 | 21106865 | The GLP-1 receptor agonists and DPP-4 inhibitors both elevate GLP-1 activity and substantially improve glycemic control. |
| 1350 | 21106865 | The GLP-1 receptor agonists are more effective in lowering blood glucose and result in substantial weight loss, whereas therapy with DPP-4 inhibitors lowers blood glucose levels to a lesser degree, and they are weight neutral. |
| 1351 | 21106865 | In addition, unlike insulin or sulfonylureas, treatment with a GLP-1 receptor agonist or a DPP-4 inhibitor has not been associated with substantial hypoglycemia. |
| 1352 | 21106866 | Incretin-based therapies, including glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors, have shown efficacy and safety in treating type 2 DM and have been reviewed in consensus treatment algorithms. |
| 1353 | 21106868 | Agents used to correct defects in the incretin system, such as glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors, offer the potential to restore glucose-dependent insulin secretion and improve β-cell function. |
| 1354 | 21130513 | Effects of multiple doses of the DPP-IV inhibitor PF-734200 on the relationship between GLP-1 and glucose in subjects with type 2 diabetes mellitus. |
| 1355 | 21130513 | A randomized, placebo-controlled study evaluated the effects multiple-doses (28 days) dipeptidyl peptidase-IV (DPP-IV) inhibitor PF-734200 on DPP-IV activity, glucose, glucagon-like peptide-1 (GLP-1), glucagon and insulin levels in 72 subjects with type 2 diabetes. |
| 1356 | 21130513 | Effects of multiple doses of the DPP-IV inhibitor PF-734200 on the relationship between GLP-1 and glucose in subjects with type 2 diabetes mellitus. |
| 1357 | 21130513 | A randomized, placebo-controlled study evaluated the effects multiple-doses (28 days) dipeptidyl peptidase-IV (DPP-IV) inhibitor PF-734200 on DPP-IV activity, glucose, glucagon-like peptide-1 (GLP-1), glucagon and insulin levels in 72 subjects with type 2 diabetes. |
| 1358 | 21139073 | Compared with OLETF rats subjected to 30% food restriction, food-satiated OLETF rats exhibited spontaneous hyperphagic obesity, insulin resistance, hyperglycemia, hyperinsulinemia, and increased plasma DPP4 activity during the early phase of the experiment (up to ∼30 wk). |
| 1359 | 21139073 | Subsequently, their plasma DPP4 activity as well as their body weight, body fat, and plasma insulin concentration declined to control levels during the late phase, resulting in excessive polyuria, proteinuria, dyslipidemia, pancreatic islet atrophy, hypoinsulinemia, and diabetes, which changed from insulin-resistant diabetes to hypoinsulinemic diabetes secondary to progressive islet insufficiency, and their fasting blood glucose level remained high. |
| 1360 | 21139073 | Since plasma DPP4 activity demonstrated significant positive correlations with body weight and the fasting plasma insulin level but not with the fasting blood glucose level during the late stage of diabetes, body fat and fasting plasma insulin levels may be useful factors for predicting the control of plasma DPP4 activity. |
| 1361 | 21139073 | In contrast, pancreatic DPP4 activity was significantly increased, and the expression of pancreatic insulin was significantly reduced in late-stage diabetic OLETF rats, suggesting that a relationship exists between the activation of pancreatic DPP4 and insulin depletion in pancreatic islet atrophy. |
| 1362 | 21139073 | DPP4 activity may play an important role in insulin homeostasis. |
| 1363 | 21139073 | Compared with OLETF rats subjected to 30% food restriction, food-satiated OLETF rats exhibited spontaneous hyperphagic obesity, insulin resistance, hyperglycemia, hyperinsulinemia, and increased plasma DPP4 activity during the early phase of the experiment (up to ∼30 wk). |
| 1364 | 21139073 | Subsequently, their plasma DPP4 activity as well as their body weight, body fat, and plasma insulin concentration declined to control levels during the late phase, resulting in excessive polyuria, proteinuria, dyslipidemia, pancreatic islet atrophy, hypoinsulinemia, and diabetes, which changed from insulin-resistant diabetes to hypoinsulinemic diabetes secondary to progressive islet insufficiency, and their fasting blood glucose level remained high. |
| 1365 | 21139073 | Since plasma DPP4 activity demonstrated significant positive correlations with body weight and the fasting plasma insulin level but not with the fasting blood glucose level during the late stage of diabetes, body fat and fasting plasma insulin levels may be useful factors for predicting the control of plasma DPP4 activity. |
| 1366 | 21139073 | In contrast, pancreatic DPP4 activity was significantly increased, and the expression of pancreatic insulin was significantly reduced in late-stage diabetic OLETF rats, suggesting that a relationship exists between the activation of pancreatic DPP4 and insulin depletion in pancreatic islet atrophy. |
| 1367 | 21139073 | DPP4 activity may play an important role in insulin homeostasis. |
| 1368 | 21139073 | Compared with OLETF rats subjected to 30% food restriction, food-satiated OLETF rats exhibited spontaneous hyperphagic obesity, insulin resistance, hyperglycemia, hyperinsulinemia, and increased plasma DPP4 activity during the early phase of the experiment (up to ∼30 wk). |
| 1369 | 21139073 | Subsequently, their plasma DPP4 activity as well as their body weight, body fat, and plasma insulin concentration declined to control levels during the late phase, resulting in excessive polyuria, proteinuria, dyslipidemia, pancreatic islet atrophy, hypoinsulinemia, and diabetes, which changed from insulin-resistant diabetes to hypoinsulinemic diabetes secondary to progressive islet insufficiency, and their fasting blood glucose level remained high. |
| 1370 | 21139073 | Since plasma DPP4 activity demonstrated significant positive correlations with body weight and the fasting plasma insulin level but not with the fasting blood glucose level during the late stage of diabetes, body fat and fasting plasma insulin levels may be useful factors for predicting the control of plasma DPP4 activity. |
| 1371 | 21139073 | In contrast, pancreatic DPP4 activity was significantly increased, and the expression of pancreatic insulin was significantly reduced in late-stage diabetic OLETF rats, suggesting that a relationship exists between the activation of pancreatic DPP4 and insulin depletion in pancreatic islet atrophy. |
| 1372 | 21139073 | DPP4 activity may play an important role in insulin homeostasis. |
| 1373 | 21139073 | Compared with OLETF rats subjected to 30% food restriction, food-satiated OLETF rats exhibited spontaneous hyperphagic obesity, insulin resistance, hyperglycemia, hyperinsulinemia, and increased plasma DPP4 activity during the early phase of the experiment (up to ∼30 wk). |
| 1374 | 21139073 | Subsequently, their plasma DPP4 activity as well as their body weight, body fat, and plasma insulin concentration declined to control levels during the late phase, resulting in excessive polyuria, proteinuria, dyslipidemia, pancreatic islet atrophy, hypoinsulinemia, and diabetes, which changed from insulin-resistant diabetes to hypoinsulinemic diabetes secondary to progressive islet insufficiency, and their fasting blood glucose level remained high. |
| 1375 | 21139073 | Since plasma DPP4 activity demonstrated significant positive correlations with body weight and the fasting plasma insulin level but not with the fasting blood glucose level during the late stage of diabetes, body fat and fasting plasma insulin levels may be useful factors for predicting the control of plasma DPP4 activity. |
| 1376 | 21139073 | In contrast, pancreatic DPP4 activity was significantly increased, and the expression of pancreatic insulin was significantly reduced in late-stage diabetic OLETF rats, suggesting that a relationship exists between the activation of pancreatic DPP4 and insulin depletion in pancreatic islet atrophy. |
| 1377 | 21139073 | DPP4 activity may play an important role in insulin homeostasis. |
| 1378 | 21139073 | Compared with OLETF rats subjected to 30% food restriction, food-satiated OLETF rats exhibited spontaneous hyperphagic obesity, insulin resistance, hyperglycemia, hyperinsulinemia, and increased plasma DPP4 activity during the early phase of the experiment (up to ∼30 wk). |
| 1379 | 21139073 | Subsequently, their plasma DPP4 activity as well as their body weight, body fat, and plasma insulin concentration declined to control levels during the late phase, resulting in excessive polyuria, proteinuria, dyslipidemia, pancreatic islet atrophy, hypoinsulinemia, and diabetes, which changed from insulin-resistant diabetes to hypoinsulinemic diabetes secondary to progressive islet insufficiency, and their fasting blood glucose level remained high. |
| 1380 | 21139073 | Since plasma DPP4 activity demonstrated significant positive correlations with body weight and the fasting plasma insulin level but not with the fasting blood glucose level during the late stage of diabetes, body fat and fasting plasma insulin levels may be useful factors for predicting the control of plasma DPP4 activity. |
| 1381 | 21139073 | In contrast, pancreatic DPP4 activity was significantly increased, and the expression of pancreatic insulin was significantly reduced in late-stage diabetic OLETF rats, suggesting that a relationship exists between the activation of pancreatic DPP4 and insulin depletion in pancreatic islet atrophy. |
| 1382 | 21139073 | DPP4 activity may play an important role in insulin homeostasis. |
| 1383 | 21154170 | Dulaglutide consists of GLP-1(7-37) covalently linked to an Fc fragment of human IgG4, thereby protecting the GLP-1 moiety from inactivation by dipeptidyl peptidase 4. |
| 1384 | 21170611 | These agents include glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-IV (DPP-IV) inhibitors. |
| 1385 | 21189532 | Janumet is a fixed-dose combination of sitagliptin, a specific inhibitor of dipeptidylpeptidase-4 that blocks the rapid degradation of so-called incretin hormones (resulting in a potentiation of insulin secretion and reduction of glucagon secretion in a glucose-dependent manner), and of metformin, a biguanide compound that reduces glucose hepatic production and slightly improves insulin sensitivity. |
| 1386 | 21198750 | Human CD26 has dipeptidyl peptidase-4 (DPP IV) enzyme activity and binds to adenosine deaminase (ADA). |
| 1387 | 21198750 | Wildtype soluble recombinant human CD26 (srhCD26), an enzyme inactive mutant (srhCD26E-) and an ADA non-binding mutant (srhCD26A-) were co-incubated in in vitro T-cell proliferation assays with peripheral blood mononuclear cells (PBMC) stimulated with phytohaemagglutinin (PHA), muromonab-CD3 or Herpes simplex virus antigen (HSV Ag). |
| 1388 | 21198750 | Thus, effects of soluble human CD26 on human T-cell proliferation are mechanistically independent of both the enzyme activity and the ADA-binding capability of sCD26. |
| 1389 | 21198750 | Human CD26 has dipeptidyl peptidase-4 (DPP IV) enzyme activity and binds to adenosine deaminase (ADA). |
| 1390 | 21198750 | Wildtype soluble recombinant human CD26 (srhCD26), an enzyme inactive mutant (srhCD26E-) and an ADA non-binding mutant (srhCD26A-) were co-incubated in in vitro T-cell proliferation assays with peripheral blood mononuclear cells (PBMC) stimulated with phytohaemagglutinin (PHA), muromonab-CD3 or Herpes simplex virus antigen (HSV Ag). |
| 1391 | 21198750 | Thus, effects of soluble human CD26 on human T-cell proliferation are mechanistically independent of both the enzyme activity and the ADA-binding capability of sCD26. |
| 1392 | 21198750 | Human CD26 has dipeptidyl peptidase-4 (DPP IV) enzyme activity and binds to adenosine deaminase (ADA). |
| 1393 | 21198750 | Wildtype soluble recombinant human CD26 (srhCD26), an enzyme inactive mutant (srhCD26E-) and an ADA non-binding mutant (srhCD26A-) were co-incubated in in vitro T-cell proliferation assays with peripheral blood mononuclear cells (PBMC) stimulated with phytohaemagglutinin (PHA), muromonab-CD3 or Herpes simplex virus antigen (HSV Ag). |
| 1394 | 21198750 | Thus, effects of soluble human CD26 on human T-cell proliferation are mechanistically independent of both the enzyme activity and the ADA-binding capability of sCD26. |
| 1395 | 21199262 | Evidence suggests that incretin-based agents, such as GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, can successfully achieve glycaemic targets and potentially provide cardiovascular and β-cell-function benefits. |
| 1396 | 21205107 | The additional efficacy seen with 50 mg twice daily [ΔHbA1c ∼- 1.1% (-12.1 mmol/mol)] relative to 50 mg once daily [ΔHbA1c ∼- 0.7% (-7.7 mmol/mol)] is attributable to an overnight effect of the evening dose of vildagliptin, with prolonged DPP-4 inhibition and elevated fasting levels of the intact and insulinotropic form of glucagon-like peptide-1 (GLP-1). |
| 1397 | 21222567 | In the past few years, the development of pharmaceutical agents that enhance the physiological effects of glucagon-like peptide-1 (GLP-1), either through GLP-1 receptor agonism (GLP-1 agonists) or by inhibiting GLP-1 degradation (dipeptidylpeptidase-4 inhibitors) has broadened the range of treatment options for individuals with type 2 diabetes. |
| 1398 | 21233599 | Newer agents, such as glucagon-like peptide-1 (GLP-1) analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors, have varying degrees of evidence to support their effects on body weight, blood pressure, and lipid levels, beyond glycated hemoglobin reduction. |
| 1399 | 21233599 | While GLP-1 agonists produce a weight loss, the DPP-4 inhibitors, conversely, appear to have a weight-neutral effect. |
| 1400 | 21233599 | Although GLP-1 agonists and DPP-4 inhibitors are at present not appropriate for primary treatment of cardiovascular risks factors, the reduction of these parameters is evidently beneficial. |
| 1401 | 21233599 | Newer agents, such as glucagon-like peptide-1 (GLP-1) analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors, have varying degrees of evidence to support their effects on body weight, blood pressure, and lipid levels, beyond glycated hemoglobin reduction. |
| 1402 | 21233599 | While GLP-1 agonists produce a weight loss, the DPP-4 inhibitors, conversely, appear to have a weight-neutral effect. |
| 1403 | 21233599 | Although GLP-1 agonists and DPP-4 inhibitors are at present not appropriate for primary treatment of cardiovascular risks factors, the reduction of these parameters is evidently beneficial. |
| 1404 | 21233599 | Newer agents, such as glucagon-like peptide-1 (GLP-1) analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors, have varying degrees of evidence to support their effects on body weight, blood pressure, and lipid levels, beyond glycated hemoglobin reduction. |
| 1405 | 21233599 | While GLP-1 agonists produce a weight loss, the DPP-4 inhibitors, conversely, appear to have a weight-neutral effect. |
| 1406 | 21233599 | Although GLP-1 agonists and DPP-4 inhibitors are at present not appropriate for primary treatment of cardiovascular risks factors, the reduction of these parameters is evidently beneficial. |
| 1407 | 21237153 | Glucagon-like peptide-1 (GLP-1)-based therapy of type 2 diabetes is executed either by GLP-1 receptor agonists, which stimulate the GLP-1 receptors, or by dipeptidyl peptidase-4 (DPP-4) inhibitors, which prevent the inactivation of endogenous GLP-1 thereby increasing the concentration of endogenous active GLP-1. |
| 1408 | 21237153 | GLP-1 activates pancreatic receptors resulting in improved glycemia through glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion. |
| 1409 | 21237153 | Furthermore, GLP-1 receptor agonists reduce body weight, whereas DPP-4 inhibitors are body weight neutral. |
| 1410 | 21237153 | Glucagon-like peptide-1 (GLP-1)-based therapy of type 2 diabetes is executed either by GLP-1 receptor agonists, which stimulate the GLP-1 receptors, or by dipeptidyl peptidase-4 (DPP-4) inhibitors, which prevent the inactivation of endogenous GLP-1 thereby increasing the concentration of endogenous active GLP-1. |
| 1411 | 21237153 | GLP-1 activates pancreatic receptors resulting in improved glycemia through glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion. |
| 1412 | 21237153 | Furthermore, GLP-1 receptor agonists reduce body weight, whereas DPP-4 inhibitors are body weight neutral. |
| 1413 | 21240332 | After metformin, with insulin in patients with severe hyperglycemia, current recommendations on treatment for type 2 diabetes suggest several pharmacotherapies, including sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 inhibitors and others. |
| 1414 | 21256171 | Preclinical and clinical studies suggest that whey proteins can reduce postprandial glucose levels and stimulate insulin release in healthy subjects and in subjects with type 2 diabetes by reducing dipeptidyl peptidase-4 (DPP-4) activity in the proximal bowel and hence increasing intact incretin levels. |
| 1415 | 21262219 | TS-021 exhibited significant inhibition selectivity against DPP-8 (>600 fold), DPP-9 (>1200 fold) and other peptidases examined (>15,000 fold). |
| 1416 | 21262219 | In Zucker fatty (fa/fa) rats, a rat model of obesity and impaired glucose tolerance, the oral administration of TS-021 resulted in the suppression of plasma DPP-IV activity and an increase in the active form of GLP-1. |
| 1417 | 21264154 | The peptide (GLP-1) increases insulin secretion while decreasing that of glucagon in response to rise in plasma glucose in addition to delay of gastric emptying time, reduction of appetite, preservation of beta-cell function, and increase in beta-cell mass all of which will contribute toward lowering of blood sugar in T2DM. |
| 1418 | 21264154 | Hence, to prolong the duration of action of endogenous GLP-1, compounds have been synthesized which inhibit the enzyme dipeptidyl peptidase-4 (DPP-4), the enzyme responsible for metabolic degradation of GLP-1. |
| 1419 | 21264154 | In this article, an attempt has been made to compile some of the established recent advances in the therapeutic utility of vildagliptin along with a discussion about the physiological role of endogenous GLP-1 and its metabolism by DPP-4. |
| 1420 | 21264154 | The peptide (GLP-1) increases insulin secretion while decreasing that of glucagon in response to rise in plasma glucose in addition to delay of gastric emptying time, reduction of appetite, preservation of beta-cell function, and increase in beta-cell mass all of which will contribute toward lowering of blood sugar in T2DM. |
| 1421 | 21264154 | Hence, to prolong the duration of action of endogenous GLP-1, compounds have been synthesized which inhibit the enzyme dipeptidyl peptidase-4 (DPP-4), the enzyme responsible for metabolic degradation of GLP-1. |
| 1422 | 21264154 | In this article, an attempt has been made to compile some of the established recent advances in the therapeutic utility of vildagliptin along with a discussion about the physiological role of endogenous GLP-1 and its metabolism by DPP-4. |
| 1423 | 21293084 | Sitagliptin and saxagliptin, both approved for use in the United States, modulate incretin physiology by inhibiting degradation of GLP-1 by the enzyme dipeptidyl peptidase-4 (DPP-4). |
| 1424 | 21293084 | Unlike the DPP-4 inhibitors, GLP-1 receptor agonist therapy also produces weight loss, an important consideration given the close association among T2DM, overweight/obesity, and cardiovascular disease. |
| 1425 | 21293084 | Sitagliptin and saxagliptin, both approved for use in the United States, modulate incretin physiology by inhibiting degradation of GLP-1 by the enzyme dipeptidyl peptidase-4 (DPP-4). |
| 1426 | 21293084 | Unlike the DPP-4 inhibitors, GLP-1 receptor agonist therapy also produces weight loss, an important consideration given the close association among T2DM, overweight/obesity, and cardiovascular disease. |
| 1427 | 21332446 | Administration of an acylated GLP-1 and GIP preparation provides added beneficial glucose-lowering and insulinotropic actions over single incretins in mice with Type 2 diabetes and obesity. |
| 1428 | 21332446 | The present study examined the glucose-lowering and insulinotropic properties of acylated GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) peptides in Type 2 diabetes and obesity. |
| 1429 | 21332446 | GLP-1, GIP, Liraglutide, N-AcGIP(Lys(37)Myr) (N-acetylGIP with myristic acid conjugated at Lys(37)), a simple combination of both peptides and a Lira-AcGIP preparation [overnight preparation of Liraglutide and N-AcGIP(Lys(37)Myr)] were incubated with DPP-IV (dipeptidyl peptidase-IV) to assess peptide stability, and BRIN-BD11 cells were used to evaluate cAMP production and insulin secretion. |
| 1430 | 21332446 | Liraglutide, N-AcGIP(Lys(37)Myr), a simple combination of both peptides and the Lira-AcGIP preparation demonstrated improved DPP-IV resistance (P<0.001), while stimulating cAMP production and insulin secretion (1.4-2-fold; P<0.001). |
| 1431 | 21332446 | These findings demonstrate that a combined preparation of the acylated GLP-1 and GIP peptides Liraglutide and N-AcGIP(Lys(37)Myr) markedly improved glucose-lowering and insulinotropic properties in diabetic obesity compared with either incretin mimetic given individually. |
| 1432 | 21332446 | Administration of an acylated GLP-1 and GIP preparation provides added beneficial glucose-lowering and insulinotropic actions over single incretins in mice with Type 2 diabetes and obesity. |
| 1433 | 21332446 | The present study examined the glucose-lowering and insulinotropic properties of acylated GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) peptides in Type 2 diabetes and obesity. |
| 1434 | 21332446 | GLP-1, GIP, Liraglutide, N-AcGIP(Lys(37)Myr) (N-acetylGIP with myristic acid conjugated at Lys(37)), a simple combination of both peptides and a Lira-AcGIP preparation [overnight preparation of Liraglutide and N-AcGIP(Lys(37)Myr)] were incubated with DPP-IV (dipeptidyl peptidase-IV) to assess peptide stability, and BRIN-BD11 cells were used to evaluate cAMP production and insulin secretion. |
| 1435 | 21332446 | Liraglutide, N-AcGIP(Lys(37)Myr), a simple combination of both peptides and the Lira-AcGIP preparation demonstrated improved DPP-IV resistance (P<0.001), while stimulating cAMP production and insulin secretion (1.4-2-fold; P<0.001). |
| 1436 | 21332446 | These findings demonstrate that a combined preparation of the acylated GLP-1 and GIP peptides Liraglutide and N-AcGIP(Lys(37)Myr) markedly improved glucose-lowering and insulinotropic properties in diabetic obesity compared with either incretin mimetic given individually. |
| 1437 | 21341455 | The place of novel agents (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) in the total pattern of treatment for type 2 DM, indications for and contraindications to their use, benefits versus traditional glucose-lowering therapy (the inestimable advantage of these drugs is no risk for hypoglycemia), and prospects for their future application are discussed. |
| 1438 | 21358699 | Such a treatment could be an incretin-based treatment with glucagon-like peptide 1 analogs, with dipeptidyl peptidase-4 inhibitors that have recently been marketed, or with sodium-glucose transporter 2 inhibitors that are being developed in phase III studies. |
| 1439 | 21371430 | Interestingly, ezetimibe significantly decreased serum dipeptidyl peptidase-4 activity and increased serum active GLP-1 in OLETF rats without altering serum total GLP-1. |
| 1440 | 21389296 | Incretin-based therapies (subcutaneously administered glucagon-like peptide-1 [GLP-1] agonists and oral dipeptidyl peptidase-4 inhibitors) represent a new mechanism of action with which to target the adverse effects of type 2 diabetes mellitus. |
| 1441 | 21389296 | Glucagon-like peptide-1 agonists are an attractive choice for patients in whom promotion of weight loss is a major consideration and the glycated hemoglobin level is moderately elevated (<8.0%) (ie, insulin is not required). |
| 1442 | 21400857 | Recently various new oral hypoglycemic agents have been developed and six different classes of agents are available now: sulfonylureas, biguanides, alpha-glucosidase inhibitors, glinides, thiazolidinediones, and dipeptidyl peptidase-4 inhibitors. |
| 1443 | 21431099 | We have moved from a situation of only having two choices, insulin and sulfonylureas, to a position of myriad choices from 11 categories of medications (insulin, sulfonylureas, biguanides, α-glucosidase inhibitors, gliptins (dipeptidyl peptidase 4 [DPP IV] inhibitors), bromocriptine, glucagon-like peptide analogues, thiazolidinediones, glinides, amylin analogues and bile acid sequestrants. |
| 1444 | 21437074 | Inhibition of dipeptidyl peptidase-4 (DPP-4) prevents the inactivation of glucagonlike peptide-1 (GLP-1). |
| 1445 | 21437074 | This increases circulating levels of active GLP-1, stimulates insulin secretion and inhibits glucagon secretion, which results in lowering of glucose levels and improvement of the glycemic control in patients with type 2 diabetes. |
| 1446 | 21437076 | Utilizing traditional agents (eg, metformin and thiazolidinediones) that do not promote hypoglycemia, in combination with newer agents such as dipeptidyl peptidase-4 inhibitors and incretin mimetics, could offer a therapeutic advantage when trying to help patients reach their hemoglobin A(1c) goal without the added risk of hypoglycemia. |
| 1447 | 21437082 | DPP-4 inhibitors elevate plasma concentrations of the incretin hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP). |
| 1448 | 21437091 | Incretin-based therapies, which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-IV (DPP-IV) inhibitors, have the potential to alter the course of type 2 diabetes and associated CVD complications. |
| 1449 | 21437091 | Advantages of these therapies include glucose-dependent enhancement of insulin secretion, infrequent instances of hypoglycemia, weight loss with GLP-1 receptor agonists, weight maintenance with DPP-IV inhibitors, decreased blood pressure, improvements in dyslipidemia, and potential beneficial effects on CV function. |
| 1450 | 21437091 | Incretin-based therapies, which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-IV (DPP-IV) inhibitors, have the potential to alter the course of type 2 diabetes and associated CVD complications. |
| 1451 | 21437091 | Advantages of these therapies include glucose-dependent enhancement of insulin secretion, infrequent instances of hypoglycemia, weight loss with GLP-1 receptor agonists, weight maintenance with DPP-IV inhibitors, decreased blood pressure, improvements in dyslipidemia, and potential beneficial effects on CV function. |
| 1452 | 21437102 | By blocking DPP-4, saxagliptin increases and prolongs the effects of incretins, a group of peptide hormones released by intestinal cells after meals, which stimulate glucose-dependent insulin secretion to lower blood glucose. |
| 1453 | 21437121 | Oral inhibitors of dipeptidyl peptidase-4 (DPP-4) raise the level of endogenous GLP-1 by inhibiting its clearance thereby lowering fasting and postprandial glucose concentrations. |
| 1454 | 21437121 | Unlike compounds which act as agonists of the GLP-1 receptor, DPP-4 inhibitors are not associated with significant effects on gastrointestinal motility, which led to a controversy around the mechanisms responsible for their glucose-lowering effects. |
| 1455 | 21437121 | Oral inhibitors of dipeptidyl peptidase-4 (DPP-4) raise the level of endogenous GLP-1 by inhibiting its clearance thereby lowering fasting and postprandial glucose concentrations. |
| 1456 | 21437121 | Unlike compounds which act as agonists of the GLP-1 receptor, DPP-4 inhibitors are not associated with significant effects on gastrointestinal motility, which led to a controversy around the mechanisms responsible for their glucose-lowering effects. |
| 1457 | 21441754 | Incretins (glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide-1 [GLP-1]) are hormones released post-meal from intestinal endocrine cells that stimulate insulin secretion and suppress postprandial glucagon secretion in a glucose-dependent manner. |
| 1458 | 21441754 | "Incretin therapies," comprising the injectable GLP-1 analogs and oral dipeptidyl peptidase-4 (DPP-4) inhibitors, are promising new therapies for use in older patients because of their consistent efficacy and low risk of hypoglycemia. |
| 1459 | 21460410 | We studied the effects of insulin, GLP-1 analogues (exendin-4), and dipeptidyl peptidase-IV (DPP-IV) inhibitor on GLP-1 cardiac receptor modulation. |
| 1460 | 21460410 | There was normalization of τ back to baseline on the CE and CM levels with insulin and DPP-IV inhibitor treatment, respectively. |
| 1461 | 21460410 | We studied the effects of insulin, GLP-1 analogues (exendin-4), and dipeptidyl peptidase-IV (DPP-IV) inhibitor on GLP-1 cardiac receptor modulation. |
| 1462 | 21460410 | There was normalization of τ back to baseline on the CE and CM levels with insulin and DPP-IV inhibitor treatment, respectively. |
| 1463 | 21475791 | In order to determine whether there is a correlation between zinc and/or copper and selected immunological parameters in patients with chronic liver disease, we investigated plasma levels of zinc and copper, concentrations of interleukin-6 (IL-6) and interferon-γ (IFN-γ), and the enzymatic activity of dipeptidyl peptidase IV (DP IV, CD26) in patients with chronic hepatitis C and in healthy control subjects. |
| 1464 | 21484567 | Incretin-based therapies consist of two classes: (1) the injectable GLP-1 receptor agonists solely acting on the GLP-1 receptor and (2) dipeptidyl-peptidase inhibitors (DPP-4 inhibitors) as oral medications raising endogenous GLP-1 and other hormone levels by inhibiting the degrading enzyme DPP-4. |
| 1465 | 21484567 | GLP-1 receptor agonists allow weight loss; DPP-4 inhibitors are weight neutral. |
| 1466 | 21484567 | Incretin-based therapies consist of two classes: (1) the injectable GLP-1 receptor agonists solely acting on the GLP-1 receptor and (2) dipeptidyl-peptidase inhibitors (DPP-4 inhibitors) as oral medications raising endogenous GLP-1 and other hormone levels by inhibiting the degrading enzyme DPP-4. |
| 1467 | 21484567 | GLP-1 receptor agonists allow weight loss; DPP-4 inhibitors are weight neutral. |
| 1468 | 21515323 | However, the half-life of GLP-1 is short in vivo due to degradation by dipeptidyl peptidase-IV (DPP-IV) and renal clearance. |
| 1469 | 21517656 | The most recent innovations in marketed T2DM therapies include 2 classes of drugs focused on the incretin system: glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. |
| 1470 | 21517658 | The current consensus statement of the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) cites efficacy and low risk of hypoglycemia in preferring GLP-1 agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors over sulfonylureas and glinides, after initial treatment with metformin. |
| 1471 | 21517658 | The guidelines prefer GLP-1 agonists over DPP-4 inhibitors because of their actions that promote weight loss and their somewhat greater effectiveness in reducing postprandial glucose excursions. |
| 1472 | 21517658 | The current consensus statement of the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) cites efficacy and low risk of hypoglycemia in preferring GLP-1 agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors over sulfonylureas and glinides, after initial treatment with metformin. |
| 1473 | 21517658 | The guidelines prefer GLP-1 agonists over DPP-4 inhibitors because of their actions that promote weight loss and their somewhat greater effectiveness in reducing postprandial glucose excursions. |
| 1474 | 21517657 | Incretin hormones, such as glucagon-like peptide-1 (GLP-1), play a crucial role in modulating insulin and glucagon secretion, as well as regulating appetite, gastric emptying, and pancreatic beta cell function. |
| 1475 | 21517657 | Incretin-based treatments for T2DM, such as GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, mimic or prolong the actions of incretin hormones and function in a glucose-dependent manner, thereby reducing hyperglycemia and avoiding hypoglycemia. |
| 1476 | 21517657 | There are important mechanistic differences between the GLP-1 receptor agonists and the DPP-4 inhibitors. |
| 1477 | 21517657 | DPP-4 inhibitors protect endogenous GLP-1 from DPP-4 degradation, thereby achieving a physiologic level of GLP-1. |
| 1478 | 21517657 | Incretin-based treatments may improve beta cell function, and, while not indicated for these effects, GLP-1 receptor agonists may also promote satiety, reduce weight, slow gastric emptying, and possibly improve hypertension and triglyceride levels; these characteristics are absent with DPP-4 inhibitors. |
| 1479 | 21517657 | Incretin hormones, such as glucagon-like peptide-1 (GLP-1), play a crucial role in modulating insulin and glucagon secretion, as well as regulating appetite, gastric emptying, and pancreatic beta cell function. |
| 1480 | 21517657 | Incretin-based treatments for T2DM, such as GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, mimic or prolong the actions of incretin hormones and function in a glucose-dependent manner, thereby reducing hyperglycemia and avoiding hypoglycemia. |
| 1481 | 21517657 | There are important mechanistic differences between the GLP-1 receptor agonists and the DPP-4 inhibitors. |
| 1482 | 21517657 | DPP-4 inhibitors protect endogenous GLP-1 from DPP-4 degradation, thereby achieving a physiologic level of GLP-1. |
| 1483 | 21517657 | Incretin-based treatments may improve beta cell function, and, while not indicated for these effects, GLP-1 receptor agonists may also promote satiety, reduce weight, slow gastric emptying, and possibly improve hypertension and triglyceride levels; these characteristics are absent with DPP-4 inhibitors. |
| 1484 | 21517657 | Incretin hormones, such as glucagon-like peptide-1 (GLP-1), play a crucial role in modulating insulin and glucagon secretion, as well as regulating appetite, gastric emptying, and pancreatic beta cell function. |
| 1485 | 21517657 | Incretin-based treatments for T2DM, such as GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, mimic or prolong the actions of incretin hormones and function in a glucose-dependent manner, thereby reducing hyperglycemia and avoiding hypoglycemia. |
| 1486 | 21517657 | There are important mechanistic differences between the GLP-1 receptor agonists and the DPP-4 inhibitors. |
| 1487 | 21517657 | DPP-4 inhibitors protect endogenous GLP-1 from DPP-4 degradation, thereby achieving a physiologic level of GLP-1. |
| 1488 | 21517657 | Incretin-based treatments may improve beta cell function, and, while not indicated for these effects, GLP-1 receptor agonists may also promote satiety, reduce weight, slow gastric emptying, and possibly improve hypertension and triglyceride levels; these characteristics are absent with DPP-4 inhibitors. |
| 1489 | 21517657 | Incretin hormones, such as glucagon-like peptide-1 (GLP-1), play a crucial role in modulating insulin and glucagon secretion, as well as regulating appetite, gastric emptying, and pancreatic beta cell function. |
| 1490 | 21517657 | Incretin-based treatments for T2DM, such as GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, mimic or prolong the actions of incretin hormones and function in a glucose-dependent manner, thereby reducing hyperglycemia and avoiding hypoglycemia. |
| 1491 | 21517657 | There are important mechanistic differences between the GLP-1 receptor agonists and the DPP-4 inhibitors. |
| 1492 | 21517657 | DPP-4 inhibitors protect endogenous GLP-1 from DPP-4 degradation, thereby achieving a physiologic level of GLP-1. |
| 1493 | 21517657 | Incretin-based treatments may improve beta cell function, and, while not indicated for these effects, GLP-1 receptor agonists may also promote satiety, reduce weight, slow gastric emptying, and possibly improve hypertension and triglyceride levels; these characteristics are absent with DPP-4 inhibitors. |
| 1494 | 21558879 | DPP-4 (CD26) inhibitor alogliptin inhibits atherosclerosis in diabetic apolipoprotein E-deficient mice. |
| 1495 | 21558879 | In this study, nondiabetic and diabetic apolipoprotein E-deficient mice were treated with DPP-4 inhibitor alogliptin for 24 weeks, and atherosclerotic lesions in aortic origins were examined. |
| 1496 | 21558879 | Furthermore, immunohistochemistry study showed that diabetes increased interleukin-6 (IL-6) and IL-1β protein expression in atherosclerotic plaques, but alogliptin treatment attenuated diabetes-augmented IL-6 and IL-1β expression. |
| 1497 | 21558879 | In consistence with the observations from the mouse models, our in vitro studies showed that alogliptin-inhibited toll-like receptor 4 (TLR-4)-mediated upregulation of IL-6, IL-1β, and other proinflammatory cytokines by mononuclear cells. |
| 1498 | 21558879 | DPP-4 (CD26) inhibitor alogliptin inhibits atherosclerosis in diabetic apolipoprotein E-deficient mice. |
| 1499 | 21558879 | In this study, nondiabetic and diabetic apolipoprotein E-deficient mice were treated with DPP-4 inhibitor alogliptin for 24 weeks, and atherosclerotic lesions in aortic origins were examined. |
| 1500 | 21558879 | Furthermore, immunohistochemistry study showed that diabetes increased interleukin-6 (IL-6) and IL-1β protein expression in atherosclerotic plaques, but alogliptin treatment attenuated diabetes-augmented IL-6 and IL-1β expression. |
| 1501 | 21558879 | In consistence with the observations from the mouse models, our in vitro studies showed that alogliptin-inhibited toll-like receptor 4 (TLR-4)-mediated upregulation of IL-6, IL-1β, and other proinflammatory cytokines by mononuclear cells. |
| 1502 | 21600946 | However, the half-life of GLP-1 is short in vivo due to rapid degradation by dipeptidyl peptidase-IV (DPP-IV) and renal clearance. |
| 1503 | 21613229 | DPP-4 inhibitor protected against β cell apoptosis, restored the β cell mass, and normalized islet morphology in Gck(+/-) mice fed SL. |
| 1504 | 21613229 | In conclusion, SL exacerbated β cell apoptosis in diabetic Gck(+/-) mice but not in euglycemic wild-type mice, and DPP-4 inhibition protected against these effects. |
| 1505 | 21613229 | DPP-4 inhibitor protected against β cell apoptosis, restored the β cell mass, and normalized islet morphology in Gck(+/-) mice fed SL. |
| 1506 | 21613229 | In conclusion, SL exacerbated β cell apoptosis in diabetic Gck(+/-) mice but not in euglycemic wild-type mice, and DPP-4 inhibition protected against these effects. |
| 1507 | 21614532 | The main objective of this study was to investigate the CD26 expression and its relationship with adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), γ-glutamyltransferase (GGT), and N-acetyl-β-glucosaminidase (NAG) activities in lymphocytes of type 2 diabetics (T2DM) patients. |
| 1508 | 21614532 | We observed a decrease in CD26 expression and a significant increase in the ADA activity in T2DM patients when compared with control subjects. |
| 1509 | 21614532 | There were no differences between activities of DPP-IV, NAG, and GGT in lymphocytes of T2DM patients and control subjects. |
| 1510 | 21614532 | Moreover, a positive correlation was found between DPPIV and ADA activities. |
| 1511 | 21614532 | The main objective of this study was to investigate the CD26 expression and its relationship with adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), γ-glutamyltransferase (GGT), and N-acetyl-β-glucosaminidase (NAG) activities in lymphocytes of type 2 diabetics (T2DM) patients. |
| 1512 | 21614532 | We observed a decrease in CD26 expression and a significant increase in the ADA activity in T2DM patients when compared with control subjects. |
| 1513 | 21614532 | There were no differences between activities of DPP-IV, NAG, and GGT in lymphocytes of T2DM patients and control subjects. |
| 1514 | 21614532 | Moreover, a positive correlation was found between DPPIV and ADA activities. |
| 1515 | 21614532 | The main objective of this study was to investigate the CD26 expression and its relationship with adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), γ-glutamyltransferase (GGT), and N-acetyl-β-glucosaminidase (NAG) activities in lymphocytes of type 2 diabetics (T2DM) patients. |
| 1516 | 21614532 | We observed a decrease in CD26 expression and a significant increase in the ADA activity in T2DM patients when compared with control subjects. |
| 1517 | 21614532 | There were no differences between activities of DPP-IV, NAG, and GGT in lymphocytes of T2DM patients and control subjects. |
| 1518 | 21614532 | Moreover, a positive correlation was found between DPPIV and ADA activities. |
| 1519 | 21614532 | The main objective of this study was to investigate the CD26 expression and its relationship with adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), γ-glutamyltransferase (GGT), and N-acetyl-β-glucosaminidase (NAG) activities in lymphocytes of type 2 diabetics (T2DM) patients. |
| 1520 | 21614532 | We observed a decrease in CD26 expression and a significant increase in the ADA activity in T2DM patients when compared with control subjects. |
| 1521 | 21614532 | There were no differences between activities of DPP-IV, NAG, and GGT in lymphocytes of T2DM patients and control subjects. |
| 1522 | 21614532 | Moreover, a positive correlation was found between DPPIV and ADA activities. |
| 1523 | 21621561 | The N-terminal alanine-extended GLP-1/IgG-Fc fusion protein confers resistance to DPP-IV and reduces serum glucose level in db/db mice. |
| 1524 | 21621561 | The aim of this study was to develop novel long-acting glucagon-like peptide 1 (GLP-1) analogs resistant to dipeptidyl peptidase-IV (DPP-IV). |
| 1525 | 21621561 | Here, we show that the Ala or Gly-extended GLP-1/IgG-Fc fusion protein is resistant to DPP-IV and has increased half-life in vivo. |
| 1526 | 21621561 | Our findings suggest that the A-GLP-1/IgG-Fc fusion protein could be a potential long-acting GLP-1 receptor agonist for the treatment of insulin-resistant type 2 diabetes. |
| 1527 | 21621561 | The N-terminal alanine-extended GLP-1/IgG-Fc fusion protein confers resistance to DPP-IV and reduces serum glucose level in db/db mice. |
| 1528 | 21621561 | The aim of this study was to develop novel long-acting glucagon-like peptide 1 (GLP-1) analogs resistant to dipeptidyl peptidase-IV (DPP-IV). |
| 1529 | 21621561 | Here, we show that the Ala or Gly-extended GLP-1/IgG-Fc fusion protein is resistant to DPP-IV and has increased half-life in vivo. |
| 1530 | 21621561 | Our findings suggest that the A-GLP-1/IgG-Fc fusion protein could be a potential long-acting GLP-1 receptor agonist for the treatment of insulin-resistant type 2 diabetes. |
| 1531 | 21621561 | The N-terminal alanine-extended GLP-1/IgG-Fc fusion protein confers resistance to DPP-IV and reduces serum glucose level in db/db mice. |
| 1532 | 21621561 | The aim of this study was to develop novel long-acting glucagon-like peptide 1 (GLP-1) analogs resistant to dipeptidyl peptidase-IV (DPP-IV). |
| 1533 | 21621561 | Here, we show that the Ala or Gly-extended GLP-1/IgG-Fc fusion protein is resistant to DPP-IV and has increased half-life in vivo. |
| 1534 | 21621561 | Our findings suggest that the A-GLP-1/IgG-Fc fusion protein could be a potential long-acting GLP-1 receptor agonist for the treatment of insulin-resistant type 2 diabetes. |
| 1535 | 21641071 | However, in vivo, the half-life of GLP-1 is short, which is caused by the degradation of dipeptidyl peptidase-IV (DPP-IV) and renal clearance. |
| 1536 | 21664938 | However, the half-life of GLP-1 is short in vivo due to degradation by dipeptidyl peptidase-IV (DPP-IV) and renal clearance. |
| 1537 | 21664938 | The long-acting anti-diabetic property of GLP715a was revealed by its increased glucose tolerance, higher HbA(1c) reduction, more efficient glucose clearance and quicker insulin stimulation upon glucose administration compared to the wild-type GLP-1 in rodents. |
| 1538 | 21680988 | As reflected in the rapidly growing body of literature and the number of glucagon-like peptide-1 and dipeptidyl peptidase-4 inhibitor (DPP-4) compounds that are either approved or in development, there is considerable interest in treatments that target the incretin axis. |
| 1539 | 21680989 | In addition to metformin, the ACCE/ACE treatment algorithm includes dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 agonists, thiazolidinediones, α-glucosidase inhibitors, sulfonylureas, and glinides. |
| 1540 | 21747834 | From theory to clinical practice in the use of GLP-1 receptor agonists and DPP-4 inhibitors therapy. |
| 1541 | 21747834 | From this perspective, vast interest has been generated by glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 inhibitors (DPP-4i). |
| 1542 | 21747834 | From theory to clinical practice in the use of GLP-1 receptor agonists and DPP-4 inhibitors therapy. |
| 1543 | 21747834 | From this perspective, vast interest has been generated by glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 inhibitors (DPP-4i). |
| 1544 | 21755761 | By inhibiting DPP-4, vildagliptin causes an increase in GLP-1, an intestinal hormone that aids in glucose homeostasis and insulin secretion. |
| 1545 | 21785903 | Fasting serum DPP-4 enzymatic activity, plasma glucose (FPG), CD26 expression on CD3+, CD4+ and CD8+ lymphocytes, HbA1c and body mass index (BMI) were assessed. |
| 1546 | 21785903 | DPP-4 enzymatic activity was determined by kinetic enzyme assay, ICA and GAD were assessed by ELISA. |
| 1547 | 21785903 | Determination of the CD26 expression on CD3+, CD4+ and CD8+ lymphocytes was performed by flow-cytometric analysis. |
| 1548 | 21785903 | Fasting serum DPP-4 activity was independent from the ICA or GAD status of patients with T1DM. |
| 1549 | 21785903 | Fasting serum DPP-4 enzymatic activity, plasma glucose (FPG), CD26 expression on CD3+, CD4+ and CD8+ lymphocytes, HbA1c and body mass index (BMI) were assessed. |
| 1550 | 21785903 | DPP-4 enzymatic activity was determined by kinetic enzyme assay, ICA and GAD were assessed by ELISA. |
| 1551 | 21785903 | Determination of the CD26 expression on CD3+, CD4+ and CD8+ lymphocytes was performed by flow-cytometric analysis. |
| 1552 | 21785903 | Fasting serum DPP-4 activity was independent from the ICA or GAD status of patients with T1DM. |
| 1553 | 21785903 | Fasting serum DPP-4 enzymatic activity, plasma glucose (FPG), CD26 expression on CD3+, CD4+ and CD8+ lymphocytes, HbA1c and body mass index (BMI) were assessed. |
| 1554 | 21785903 | DPP-4 enzymatic activity was determined by kinetic enzyme assay, ICA and GAD were assessed by ELISA. |
| 1555 | 21785903 | Determination of the CD26 expression on CD3+, CD4+ and CD8+ lymphocytes was performed by flow-cytometric analysis. |
| 1556 | 21785903 | Fasting serum DPP-4 activity was independent from the ICA or GAD status of patients with T1DM. |
| 1557 | 21785903 | Fasting serum DPP-4 enzymatic activity, plasma glucose (FPG), CD26 expression on CD3+, CD4+ and CD8+ lymphocytes, HbA1c and body mass index (BMI) were assessed. |
| 1558 | 21785903 | DPP-4 enzymatic activity was determined by kinetic enzyme assay, ICA and GAD were assessed by ELISA. |
| 1559 | 21785903 | Determination of the CD26 expression on CD3+, CD4+ and CD8+ lymphocytes was performed by flow-cytometric analysis. |
| 1560 | 21785903 | Fasting serum DPP-4 activity was independent from the ICA or GAD status of patients with T1DM. |
| 1561 | 21887518 | Altered proportions of naïve, central memory and terminally differentiated central memory subsets among CD4+ and CD8 + T cells expressing CD26 in patients with type 1 diabetes. |
| 1562 | 21887518 | In peripheral blood from 55 patients with type 1 diabetes and 20 healthy controls, CD4(+) and CD8(+) T cells expressing CD26 were differentiated into naïve (N, CD45RA(+)CCR7(+)), central memory (CM, CD45RA(-)CCR7(+)), effector memory (EM, CD45RA(-)CCR7(-)), and terminally differentiated effector memory (TEMRA, CD45RA(+)CCR7(-)). |
| 1563 | 21887518 | In type 1 diabetes, CD4(+) and CD8(+) T cells expressing CD26 showed a distinctive differentiation profile: percentages and absolute numbers of CM and N cells were reduced, whereas those of TEMRA cells were markedly increased. |
| 1564 | 21887518 | Altered proportions of naïve, central memory and terminally differentiated central memory subsets among CD4+ and CD8 + T cells expressing CD26 in patients with type 1 diabetes. |
| 1565 | 21887518 | In peripheral blood from 55 patients with type 1 diabetes and 20 healthy controls, CD4(+) and CD8(+) T cells expressing CD26 were differentiated into naïve (N, CD45RA(+)CCR7(+)), central memory (CM, CD45RA(-)CCR7(+)), effector memory (EM, CD45RA(-)CCR7(-)), and terminally differentiated effector memory (TEMRA, CD45RA(+)CCR7(-)). |
| 1566 | 21887518 | In type 1 diabetes, CD4(+) and CD8(+) T cells expressing CD26 showed a distinctive differentiation profile: percentages and absolute numbers of CM and N cells were reduced, whereas those of TEMRA cells were markedly increased. |
| 1567 | 21887518 | Altered proportions of naïve, central memory and terminally differentiated central memory subsets among CD4+ and CD8 + T cells expressing CD26 in patients with type 1 diabetes. |
| 1568 | 21887518 | In peripheral blood from 55 patients with type 1 diabetes and 20 healthy controls, CD4(+) and CD8(+) T cells expressing CD26 were differentiated into naïve (N, CD45RA(+)CCR7(+)), central memory (CM, CD45RA(-)CCR7(+)), effector memory (EM, CD45RA(-)CCR7(-)), and terminally differentiated effector memory (TEMRA, CD45RA(+)CCR7(-)). |
| 1569 | 21887518 | In type 1 diabetes, CD4(+) and CD8(+) T cells expressing CD26 showed a distinctive differentiation profile: percentages and absolute numbers of CM and N cells were reduced, whereas those of TEMRA cells were markedly increased. |
| 1570 | 21898126 | Miglitol and dipeptidyl peptidase-4 inhibitors, such as sitagliptin, enhance plasma active GLP-1 concentrations via different mechanisms; therefore, combined therapy with these agents was more effective than monotherapy. |
| 1571 | 21898126 | We measured the plasma glucose, serum insulin and glucagon, plasma active GLP-1, and total glucose-dependent insulinotropic polypeptide levels before breakfast, at 120 min after breakfast, before lunch, and 60 and 120 min after lunch in patients with diabetes who are receiving sitagliptin. |
| 1572 | 21958333 | The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) stimulate glucose-induced insulin secretion; however, in patients with type 2 diabetes, the incretin system is impaired by loss of the insulinotropic effects of GIP as well as a possible reduction in secretion of GLP-1. |
| 1573 | 21958333 | The currently available incretin-based therapies, GLP-1 receptor agonists (incretin mimetics) and dipeptidyl peptidase-4 (DPP-4) inhibitors (CD26 antigen inhibitors) [incretin enhancers], are safe and effective in the treatment of type 2 diabetes. |
| 1574 | 21958333 | Therapies that directly target intestinal L cells to stimulate secretion of endogenous GLP-1 could possibly prove more effective than treatment with GLP-1 receptor agonists and DPP-4 inhibitors. |
| 1575 | 21958333 | Potential new approaches to modifying intestinal GLP-1 secretion in patients with type 2 diabetes include G-protein-coupled receptor (GPCR) agonists, α-glucosidase inhibitors, peroxisome proliferator-activated receptor (PPAR) agonists, metformin, bile acid mimetics and bile acid sequestrants. |
| 1576 | 21958333 | Both the GPCR agonist AR231453 and the novel bile acid mimetic INT-777 have been shown to stimulate GLP-1 release, leading to increased insulin secretion and improved glucose tolerance in mice. |
| 1577 | 21958333 | Similarly, a study in insulin-resistant rats demonstrated that the bile acid sequestrant colesevelam increased GLP-1 secretion and improved glucose levels and insulin resistance. |
| 1578 | 21958333 | Evidence suggests that GPCR agonists, α-glucosidase inhibitors, PPAR agonists, metformin, bile acid mimetics and bile acid sequestrants may represent a new approach to management of type 2 diabetes via modification of endogenous GLP-1 secretion. |
| 1579 | 21958333 | The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) stimulate glucose-induced insulin secretion; however, in patients with type 2 diabetes, the incretin system is impaired by loss of the insulinotropic effects of GIP as well as a possible reduction in secretion of GLP-1. |
| 1580 | 21958333 | The currently available incretin-based therapies, GLP-1 receptor agonists (incretin mimetics) and dipeptidyl peptidase-4 (DPP-4) inhibitors (CD26 antigen inhibitors) [incretin enhancers], are safe and effective in the treatment of type 2 diabetes. |
| 1581 | 21958333 | Therapies that directly target intestinal L cells to stimulate secretion of endogenous GLP-1 could possibly prove more effective than treatment with GLP-1 receptor agonists and DPP-4 inhibitors. |
| 1582 | 21958333 | Potential new approaches to modifying intestinal GLP-1 secretion in patients with type 2 diabetes include G-protein-coupled receptor (GPCR) agonists, α-glucosidase inhibitors, peroxisome proliferator-activated receptor (PPAR) agonists, metformin, bile acid mimetics and bile acid sequestrants. |
| 1583 | 21958333 | Both the GPCR agonist AR231453 and the novel bile acid mimetic INT-777 have been shown to stimulate GLP-1 release, leading to increased insulin secretion and improved glucose tolerance in mice. |
| 1584 | 21958333 | Similarly, a study in insulin-resistant rats demonstrated that the bile acid sequestrant colesevelam increased GLP-1 secretion and improved glucose levels and insulin resistance. |
| 1585 | 21958333 | Evidence suggests that GPCR agonists, α-glucosidase inhibitors, PPAR agonists, metformin, bile acid mimetics and bile acid sequestrants may represent a new approach to management of type 2 diabetes via modification of endogenous GLP-1 secretion. |
| 1586 | 21966329 | It has been shown that the naturally occurring gut hormones incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) can preserve the morphology and function of pancreatic beta cell. |
| 1587 | 21966329 | In addition, GIP and GLP-1 act on insulin receptors to facilitate insulin-receptor binding, resulting in optimal glucose metabolism. |
| 1588 | 21966329 | The paper also identified and reviewed a number of inhibitors, which can block dipeptidyl peptidase 4 (DPP-4), the enzyme responsible for the rapid degradation of GLP-1. |
| 1589 | 21971158 | Glucagon-like peptide-1(7-36NH2) (GLP-1) is secreted by the intestinal L cell in response to both nutrient and neural stimulation, resulting in enhanced glucose-dependent insulin secretion. |
| 1590 | 21971158 | In contrast, pretreatment with the gastrin-releasing peptide antagonist, RC-3095 (100 μg/kg, sc), reduced the GLP-1 response to metformin, by 55 ± 6% (P < 0.01) at 30 min. |
| 1591 | 21971158 | These studies elucidate the mechanism underlying metformin-induced GLP-1 secretion and highlight the benefits of using metformin with dipeptidylpeptidase-IV inhibitors in patients with type 2 diabetes. |
| 1592 | 21996520 | 7-Oxopyrrolopyridine-derived DPP4 inhibitors-mitigation of CYP and hERG liabilities via introduction of polar functionalities in the active site. |
| 1593 | 21996520 | Compound (+)-3t, with a K(i) against DPP4, DPP8, and DPP9 of 0.37 nM, 2.2, and 5.7 μM, respectively, showed a significant improvement in insulin response after single doses of 3 and 10 μmol/kg in ob/ob mice. |
| 1594 | 22015634 | The enzyme dipeptidyl peptidase-IV (DPP-4) inactivates the incretin hormone glucagon-like peptide-1 (GLP-1). |
| 1595 | 22015634 | GLP-1 has therapeutic effects in patients with type 2 diabetes, but its potential is limited by a short half-life, DPP-4 inhibition is a promising approach to diabetes treatment. |
| 1596 | 22015634 | This study examined chronic (once-a-day dosing for 8 weeks) effects of the DPP-4 inhibitor PKF-275-055 (1, 3, and 10mg/kg) on β-cell regeneration and plasma DPP-IV activity, intact GLP-1, glucose, and insulin after an oral glucose load in neonatal wistar rats injected with streptozotocin (STZ) (n2-STZ model), a recognized model of type 2 diabetes. |
| 1597 | 22015634 | In streptozotocin induced diabetic rats, PKF-275-055 (3, and 10mg/kg) significantly reduced glucose excursion during the oral glucose tolerance test conducted 2h and 10h after administration, with increases in plasma insulin and active glucagon-like peptide-1 (GLP-1) levels and significantly inhibited (> 50% inhibition) plasma DPP-IV activity during both the 1st and 2nd OGTT in diabetic rats. |
| 1598 | 22015634 | The enzyme dipeptidyl peptidase-IV (DPP-4) inactivates the incretin hormone glucagon-like peptide-1 (GLP-1). |
| 1599 | 22015634 | GLP-1 has therapeutic effects in patients with type 2 diabetes, but its potential is limited by a short half-life, DPP-4 inhibition is a promising approach to diabetes treatment. |
| 1600 | 22015634 | This study examined chronic (once-a-day dosing for 8 weeks) effects of the DPP-4 inhibitor PKF-275-055 (1, 3, and 10mg/kg) on β-cell regeneration and plasma DPP-IV activity, intact GLP-1, glucose, and insulin after an oral glucose load in neonatal wistar rats injected with streptozotocin (STZ) (n2-STZ model), a recognized model of type 2 diabetes. |
| 1601 | 22015634 | In streptozotocin induced diabetic rats, PKF-275-055 (3, and 10mg/kg) significantly reduced glucose excursion during the oral glucose tolerance test conducted 2h and 10h after administration, with increases in plasma insulin and active glucagon-like peptide-1 (GLP-1) levels and significantly inhibited (> 50% inhibition) plasma DPP-IV activity during both the 1st and 2nd OGTT in diabetic rats. |
| 1602 | 22015634 | The enzyme dipeptidyl peptidase-IV (DPP-4) inactivates the incretin hormone glucagon-like peptide-1 (GLP-1). |
| 1603 | 22015634 | GLP-1 has therapeutic effects in patients with type 2 diabetes, but its potential is limited by a short half-life, DPP-4 inhibition is a promising approach to diabetes treatment. |
| 1604 | 22015634 | This study examined chronic (once-a-day dosing for 8 weeks) effects of the DPP-4 inhibitor PKF-275-055 (1, 3, and 10mg/kg) on β-cell regeneration and plasma DPP-IV activity, intact GLP-1, glucose, and insulin after an oral glucose load in neonatal wistar rats injected with streptozotocin (STZ) (n2-STZ model), a recognized model of type 2 diabetes. |
| 1605 | 22015634 | In streptozotocin induced diabetic rats, PKF-275-055 (3, and 10mg/kg) significantly reduced glucose excursion during the oral glucose tolerance test conducted 2h and 10h after administration, with increases in plasma insulin and active glucagon-like peptide-1 (GLP-1) levels and significantly inhibited (> 50% inhibition) plasma DPP-IV activity during both the 1st and 2nd OGTT in diabetic rats. |
| 1606 | 22015634 | The enzyme dipeptidyl peptidase-IV (DPP-4) inactivates the incretin hormone glucagon-like peptide-1 (GLP-1). |
| 1607 | 22015634 | GLP-1 has therapeutic effects in patients with type 2 diabetes, but its potential is limited by a short half-life, DPP-4 inhibition is a promising approach to diabetes treatment. |
| 1608 | 22015634 | This study examined chronic (once-a-day dosing for 8 weeks) effects of the DPP-4 inhibitor PKF-275-055 (1, 3, and 10mg/kg) on β-cell regeneration and plasma DPP-IV activity, intact GLP-1, glucose, and insulin after an oral glucose load in neonatal wistar rats injected with streptozotocin (STZ) (n2-STZ model), a recognized model of type 2 diabetes. |
| 1609 | 22015634 | In streptozotocin induced diabetic rats, PKF-275-055 (3, and 10mg/kg) significantly reduced glucose excursion during the oral glucose tolerance test conducted 2h and 10h after administration, with increases in plasma insulin and active glucagon-like peptide-1 (GLP-1) levels and significantly inhibited (> 50% inhibition) plasma DPP-IV activity during both the 1st and 2nd OGTT in diabetic rats. |
| 1610 | 22056790 | DPP-IV in serum degrades the incretin hormones which stimulate β-cell insulin secretion. |
| 1611 | 22056790 | DPP-IV inhibitors, as incretin enhancers, cause an increase in glucose-dependent insulin secretion, and are applied for the treatment of diabetes mellitus. |
| 1612 | 22056790 | DPP-IV in serum degrades the incretin hormones which stimulate β-cell insulin secretion. |
| 1613 | 22056790 | DPP-IV inhibitors, as incretin enhancers, cause an increase in glucose-dependent insulin secretion, and are applied for the treatment of diabetes mellitus. |
| 1614 | 22056828 | Incretin-based therapies, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, have limited use in hospitals, but may be suitable for the transition to outpatient treatment. |
| 1615 | 22122222 | Both the ADA and AACE recommend metformin as a firstline oral agent; however, the ADA supports early use of sulfonylureas or insulin in patients who do not reach their target A1C goal, whereas the AACE recommends earlier and more frequent use of the newer incretin agents-glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. |
| 1616 | 22155545 | Relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets: effects of DPP-IV inhibitor vildagliptin. |
| 1617 | 22155545 | The aim of the present study was to evaluate the relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets, using dipeptidyl peptidase-IV (DPP-IV) inhibitor vildagliptin. |
| 1618 | 22155545 | Relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets: effects of DPP-IV inhibitor vildagliptin. |
| 1619 | 22155545 | The aim of the present study was to evaluate the relationships between the islets blood flow, nitric oxide, insulin, and cytosolic calcium in rat pancreatic islets, using dipeptidyl peptidase-IV (DPP-IV) inhibitor vildagliptin. |
| 1620 | 22186413 | Novel biological action of the dipeptidylpeptidase-IV inhibitor, sitagliptin, as a glucagon-like peptide-1 secretagogue. |
| 1621 | 22186413 | The dipeptidylpeptidase-IV (DPP-IV) inhibitor, sitagliptin, prevents GLP-1 degradation and is used in the clinic to treat patients with type 2 diabetes mellitus, leading to improved glycated hemoglobin levels. |
| 1622 | 22186413 | However, MK0626 (1-50 μM), a structurally unrelated inhibitor of DPP-IV, did not affect GLP-1 secretion in either model. |
| 1623 | 22186413 | Pretreatment of mGLUTag cells with protein kinase A (H89 and protein kinase inhibitor) or MAPK kinase-ERK1/2 (PD98059 and U0126) inhibitors prevented sitagliptin-induced GLP-1 secretion (P < 0.05-0.01). |
| 1624 | 22186413 | These studies demonstrate, for the first time, that sitagliptin exerts direct, DPP-IV-independent effects on intestinal L cells, activating cAMP and ERK1/2 signaling and stimulating total GLP-1 secretion. |
| 1625 | 22186413 | Novel biological action of the dipeptidylpeptidase-IV inhibitor, sitagliptin, as a glucagon-like peptide-1 secretagogue. |
| 1626 | 22186413 | The dipeptidylpeptidase-IV (DPP-IV) inhibitor, sitagliptin, prevents GLP-1 degradation and is used in the clinic to treat patients with type 2 diabetes mellitus, leading to improved glycated hemoglobin levels. |
| 1627 | 22186413 | However, MK0626 (1-50 μM), a structurally unrelated inhibitor of DPP-IV, did not affect GLP-1 secretion in either model. |
| 1628 | 22186413 | Pretreatment of mGLUTag cells with protein kinase A (H89 and protein kinase inhibitor) or MAPK kinase-ERK1/2 (PD98059 and U0126) inhibitors prevented sitagliptin-induced GLP-1 secretion (P < 0.05-0.01). |
| 1629 | 22186413 | These studies demonstrate, for the first time, that sitagliptin exerts direct, DPP-IV-independent effects on intestinal L cells, activating cAMP and ERK1/2 signaling and stimulating total GLP-1 secretion. |
| 1630 | 22186413 | Novel biological action of the dipeptidylpeptidase-IV inhibitor, sitagliptin, as a glucagon-like peptide-1 secretagogue. |
| 1631 | 22186413 | The dipeptidylpeptidase-IV (DPP-IV) inhibitor, sitagliptin, prevents GLP-1 degradation and is used in the clinic to treat patients with type 2 diabetes mellitus, leading to improved glycated hemoglobin levels. |
| 1632 | 22186413 | However, MK0626 (1-50 μM), a structurally unrelated inhibitor of DPP-IV, did not affect GLP-1 secretion in either model. |
| 1633 | 22186413 | Pretreatment of mGLUTag cells with protein kinase A (H89 and protein kinase inhibitor) or MAPK kinase-ERK1/2 (PD98059 and U0126) inhibitors prevented sitagliptin-induced GLP-1 secretion (P < 0.05-0.01). |
| 1634 | 22186413 | These studies demonstrate, for the first time, that sitagliptin exerts direct, DPP-IV-independent effects on intestinal L cells, activating cAMP and ERK1/2 signaling and stimulating total GLP-1 secretion. |
| 1635 | 22197148 | Several clinical trials also showed a consistent reduction in HbA(1c) when DPP-4 inhibitors were added to basal insulin therapy, with no increased risk of hypoglycaemia. |
| 1636 | 22198311 | Excretion of the dipeptidyl peptidase-4 inhibitor linagliptin in rats is primarily by biliary excretion and P-gp-mediated efflux. |
| 1637 | 22233527 | Glucagon-like peptide-1 (GLP-1), a gut-derived hormone secreted in response to nutrients, has several glucose and weight regulating actions including enhancement of glucose-stimulated insulin secretion, suppression of glucagon secretion, slowing of gastric emptying and reduction in food intake. |
| 1638 | 22233527 | However, GLP-1 has significant limitations as a therapeutic due to its rapid degradation (plasma half-life of 1-2 min) by dipeptidyl peptidase-4 (DPP-4). |
| 1639 | 22233527 | Two main classes of GLP-1-mediated therapies are now in use: DPP-4 inhibitors that reduce the degradation of GLP-1 and DPP-4-resistant GLP-1 receptor (GLP-1R) agonists. |
| 1640 | 22233527 | This review summarizes the similarities and differences among DPP-4 inhibitors, short-acting GLP-1R agonists and long-acting GLP-1R agonists. |
| 1641 | 22233527 | Glucagon-like peptide-1 (GLP-1), a gut-derived hormone secreted in response to nutrients, has several glucose and weight regulating actions including enhancement of glucose-stimulated insulin secretion, suppression of glucagon secretion, slowing of gastric emptying and reduction in food intake. |
| 1642 | 22233527 | However, GLP-1 has significant limitations as a therapeutic due to its rapid degradation (plasma half-life of 1-2 min) by dipeptidyl peptidase-4 (DPP-4). |
| 1643 | 22233527 | Two main classes of GLP-1-mediated therapies are now in use: DPP-4 inhibitors that reduce the degradation of GLP-1 and DPP-4-resistant GLP-1 receptor (GLP-1R) agonists. |
| 1644 | 22233527 | This review summarizes the similarities and differences among DPP-4 inhibitors, short-acting GLP-1R agonists and long-acting GLP-1R agonists. |
| 1645 | 22233527 | Glucagon-like peptide-1 (GLP-1), a gut-derived hormone secreted in response to nutrients, has several glucose and weight regulating actions including enhancement of glucose-stimulated insulin secretion, suppression of glucagon secretion, slowing of gastric emptying and reduction in food intake. |
| 1646 | 22233527 | However, GLP-1 has significant limitations as a therapeutic due to its rapid degradation (plasma half-life of 1-2 min) by dipeptidyl peptidase-4 (DPP-4). |
| 1647 | 22233527 | Two main classes of GLP-1-mediated therapies are now in use: DPP-4 inhibitors that reduce the degradation of GLP-1 and DPP-4-resistant GLP-1 receptor (GLP-1R) agonists. |
| 1648 | 22233527 | This review summarizes the similarities and differences among DPP-4 inhibitors, short-acting GLP-1R agonists and long-acting GLP-1R agonists. |
| 1649 | 22262069 | There are two classes of incretin agents: the dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon like peptide 1 (GLP-1) receptor agonists. |
| 1650 | 22262069 | The ultimate goal of agents within both of these classes is to increase GLP-1 signaling, which results in augmented glucose-induced insulin secretion, inhibition of glucagon secretion, and decreased appetite. |
| 1651 | 22262069 | In contrast, DPP-4 inhibitors result in a less dramatic increase in GLP-1 levels; therefore, they are weight neutral. |
| 1652 | 22262069 | There are two classes of incretin agents: the dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon like peptide 1 (GLP-1) receptor agonists. |
| 1653 | 22262069 | The ultimate goal of agents within both of these classes is to increase GLP-1 signaling, which results in augmented glucose-induced insulin secretion, inhibition of glucagon secretion, and decreased appetite. |
| 1654 | 22262069 | In contrast, DPP-4 inhibitors result in a less dramatic increase in GLP-1 levels; therefore, they are weight neutral. |
| 1655 | 22267300 | Incretin-based agents, including glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, have become important options in the therapeutic paradigm for patients with type 2 diabetes mellitus. |
| 1656 | 22267300 | The author reviews physiologic mechanisms of the incretin system and discusses the practical application of GLP-1 receptor agonists and DPP-4 inhibitors in improving GLP-1 dynamics in patients with type 2 diabetes mellitus. |
| 1657 | 22267300 | Incretin-based agents, including glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, have become important options in the therapeutic paradigm for patients with type 2 diabetes mellitus. |
| 1658 | 22267300 | The author reviews physiologic mechanisms of the incretin system and discusses the practical application of GLP-1 receptor agonists and DPP-4 inhibitors in improving GLP-1 dynamics in patients with type 2 diabetes mellitus. |
| 1659 | 22323472 | Glucagon-like peptide-1 (GLP-1) is an incretin hormone that enhances glucose-stimulated insulin secretion and exerts direct and indirect actions on the cardiovascular system. |
| 1660 | 22323472 | GLP-1 and its related incretin hormone, glucose-dependent insulinotropic polypeptide, are rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4), a key determinant of incretin bioactivity. |
| 1661 | 22323472 | Two classes of medications that enhance incretin action, GLP-1 receptor (GLP-1R) agonists and DPP-4 inhibitors, are used for the treatment of type 2 diabetes mellitus. |
| 1662 | 22323472 | We review herein the cardiovascular biology of GLP-1R agonists and DPP-4 inhibitors, including direct and indirect effects on cardiomyocytes, blood vessels, adipocytes, the control of blood pressure, and postprandial lipoprotein secretion. |
| 1663 | 22323472 | Both GLP-1R activation and DPP-4 inhibition exert multiple cardioprotective actions in preclinical models of cardiovascular dysfunction, and short-term studies in human subjects appear to demonstrate modest yet beneficial actions on cardiac function in subjects with ischemic heart disease. |
| 1664 | 22323472 | Glucagon-like peptide-1 (GLP-1) is an incretin hormone that enhances glucose-stimulated insulin secretion and exerts direct and indirect actions on the cardiovascular system. |
| 1665 | 22323472 | GLP-1 and its related incretin hormone, glucose-dependent insulinotropic polypeptide, are rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4), a key determinant of incretin bioactivity. |
| 1666 | 22323472 | Two classes of medications that enhance incretin action, GLP-1 receptor (GLP-1R) agonists and DPP-4 inhibitors, are used for the treatment of type 2 diabetes mellitus. |
| 1667 | 22323472 | We review herein the cardiovascular biology of GLP-1R agonists and DPP-4 inhibitors, including direct and indirect effects on cardiomyocytes, blood vessels, adipocytes, the control of blood pressure, and postprandial lipoprotein secretion. |
| 1668 | 22323472 | Both GLP-1R activation and DPP-4 inhibition exert multiple cardioprotective actions in preclinical models of cardiovascular dysfunction, and short-term studies in human subjects appear to demonstrate modest yet beneficial actions on cardiac function in subjects with ischemic heart disease. |
| 1669 | 22323472 | Glucagon-like peptide-1 (GLP-1) is an incretin hormone that enhances glucose-stimulated insulin secretion and exerts direct and indirect actions on the cardiovascular system. |
| 1670 | 22323472 | GLP-1 and its related incretin hormone, glucose-dependent insulinotropic polypeptide, are rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4), a key determinant of incretin bioactivity. |
| 1671 | 22323472 | Two classes of medications that enhance incretin action, GLP-1 receptor (GLP-1R) agonists and DPP-4 inhibitors, are used for the treatment of type 2 diabetes mellitus. |
| 1672 | 22323472 | We review herein the cardiovascular biology of GLP-1R agonists and DPP-4 inhibitors, including direct and indirect effects on cardiomyocytes, blood vessels, adipocytes, the control of blood pressure, and postprandial lipoprotein secretion. |
| 1673 | 22323472 | Both GLP-1R activation and DPP-4 inhibition exert multiple cardioprotective actions in preclinical models of cardiovascular dysfunction, and short-term studies in human subjects appear to demonstrate modest yet beneficial actions on cardiac function in subjects with ischemic heart disease. |
| 1674 | 22323472 | Glucagon-like peptide-1 (GLP-1) is an incretin hormone that enhances glucose-stimulated insulin secretion and exerts direct and indirect actions on the cardiovascular system. |
| 1675 | 22323472 | GLP-1 and its related incretin hormone, glucose-dependent insulinotropic polypeptide, are rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4), a key determinant of incretin bioactivity. |
| 1676 | 22323472 | Two classes of medications that enhance incretin action, GLP-1 receptor (GLP-1R) agonists and DPP-4 inhibitors, are used for the treatment of type 2 diabetes mellitus. |
| 1677 | 22323472 | We review herein the cardiovascular biology of GLP-1R agonists and DPP-4 inhibitors, including direct and indirect effects on cardiomyocytes, blood vessels, adipocytes, the control of blood pressure, and postprandial lipoprotein secretion. |
| 1678 | 22323472 | Both GLP-1R activation and DPP-4 inhibition exert multiple cardioprotective actions in preclinical models of cardiovascular dysfunction, and short-term studies in human subjects appear to demonstrate modest yet beneficial actions on cardiac function in subjects with ischemic heart disease. |
| 1679 | 22324384 | According to the latest American Diabetes Association guidelines, lowering glycated hemoglobin (HbA(1c)) to below or around 7% has been shown to reduce microvascular and neuropathic complications of diabetes and, if implemented soon after the diagnosis of diabetes, is associated with long-term reduction in macrovascular disease. |
| 1680 | 22324384 | Recently a new class of antidiabetes drugs has been developed, dipeptidyl peptidase-4 (DPP-4) inhibitors, which act by inhibiting DPP-4, the enzyme that inactivates glucagon-like peptide-1 (GLP-1). |
| 1681 | 22324384 | Through the inhibition of DPP-4, DPP-4 inhibitors enhance the effects of GLP-1 and glucose-dependent insulinotropic peptide, increasing glucose-mediated insulin secretion and suppressing glucagon secretion. |
| 1682 | 22324384 | According to the latest American Diabetes Association guidelines, lowering glycated hemoglobin (HbA(1c)) to below or around 7% has been shown to reduce microvascular and neuropathic complications of diabetes and, if implemented soon after the diagnosis of diabetes, is associated with long-term reduction in macrovascular disease. |
| 1683 | 22324384 | Recently a new class of antidiabetes drugs has been developed, dipeptidyl peptidase-4 (DPP-4) inhibitors, which act by inhibiting DPP-4, the enzyme that inactivates glucagon-like peptide-1 (GLP-1). |
| 1684 | 22324384 | Through the inhibition of DPP-4, DPP-4 inhibitors enhance the effects of GLP-1 and glucose-dependent insulinotropic peptide, increasing glucose-mediated insulin secretion and suppressing glucagon secretion. |
| 1685 | 22363882 | Berberine lowered plasma free fatty acids and C-reactive protein levels without affecting plasma insulin levels. |
| 1686 | 22363882 | Furthermore, berberine inhibited dipeptidyl peptidase-4 and protein tyrosine phosphatase-1B activities. |
| 1687 | 22411425 | Moreover, hypoglycemia is a frequent side effect of therapeutic treatment with insulin, sulfonylureas or glinides, while other treatments (metformin, acarbose, thiazolidinediones, glucagon-like peptide-1 [GLP-1] receptor agonists, and dipeptidyl peptidase-4 [DPP4] inhibitors) are capable of reducing hyperglycemia without inducing hypoglycemia. |
| 1688 | 22411425 | Available options include sulfonylureas, meglitinides, alfa-glucosidase inhibitors, pioglitazone, insulin, GLP-1 receptor agonists, and DPP-4 inhibitors. |
| 1689 | 22411425 | These hormones potentiate the acute effects of glucose on pancreatic alfa and beta cells, thus stimulating insulin secretion, and only GLP-1 inhibits glucagon secretion in a glucose-dependent manner (that is, only when glucose levels are increased); as a result, they reduce hyperglycemia with virtually no hypoglycemic risk. |
| 1690 | 22411425 | Moreover, hypoglycemia is a frequent side effect of therapeutic treatment with insulin, sulfonylureas or glinides, while other treatments (metformin, acarbose, thiazolidinediones, glucagon-like peptide-1 [GLP-1] receptor agonists, and dipeptidyl peptidase-4 [DPP4] inhibitors) are capable of reducing hyperglycemia without inducing hypoglycemia. |
| 1691 | 22411425 | Available options include sulfonylureas, meglitinides, alfa-glucosidase inhibitors, pioglitazone, insulin, GLP-1 receptor agonists, and DPP-4 inhibitors. |
| 1692 | 22411425 | These hormones potentiate the acute effects of glucose on pancreatic alfa and beta cells, thus stimulating insulin secretion, and only GLP-1 inhibits glucagon secretion in a glucose-dependent manner (that is, only when glucose levels are increased); as a result, they reduce hyperglycemia with virtually no hypoglycemic risk. |
| 1693 | 22425330 | They exert their action through inhibition of the catabolism of locally secreted incretins such as glucagon-like peptide-4 (GLP-4) and glucose-dependent insulinotropic polypeptide (GIP) by inhibiting enzyme DPP-4. |
| 1694 | 22425330 | GLP-1 and GIP are secreted from the gastrointestinal tract in response to food intake. |
| 1695 | 22425330 | GLP-1 is secreted from L cells present in the mucosa of the small intestine and colon, whereas GIP is secreted from K cells of the jejunum. |
| 1696 | 22473614 | We have further determined that MLR-1023 did not activate peroxisome proliferator-activated α, δ, and γ receptors or glucagon-like peptide-1 receptors or inhibit dipeptidyl peptidase-4 or α-glucosidase enzyme activity. |
| 1697 | 22482239 | Linagliptin (Trajenta) is a selective inhibitor of dipeptidyl peptidase-4, an enzyme that degrades two incretin hormones, GLP-1 ("Glucagon-Like Peptide-1") and GIP ("Glucose-dependent Insulinotropic Polypeptide"). |
| 1698 | 22486277 | Effects of chronic treatment with metformin on dipeptidyl peptidase-4 activity, glucagon-like peptide 1 and ghrelin in obese patients with Type 2 diabetes mellitus. |
| 1699 | 22493041 | In recent years, new and effective therapeutic agents for blood glucose control have been added to standard diabetes therapies: dipeptidyl peptidase-4 (DPP-4) inhibitors, which prolong the bioavailability of the endogenously secreted incretin hormone glucagon-like peptide-1 (GLP-1). |
| 1700 | 22493041 | Oral administration of the DPP-4 inhibitor linagliptin strongly reduced DPP-4 activity, stabilized active GLP-1 in chronic wounds, and improved healing in ob/ob mice. |
| 1701 | 22493041 | In recent years, new and effective therapeutic agents for blood glucose control have been added to standard diabetes therapies: dipeptidyl peptidase-4 (DPP-4) inhibitors, which prolong the bioavailability of the endogenously secreted incretin hormone glucagon-like peptide-1 (GLP-1). |
| 1702 | 22493041 | Oral administration of the DPP-4 inhibitor linagliptin strongly reduced DPP-4 activity, stabilized active GLP-1 in chronic wounds, and improved healing in ob/ob mice. |
| 1703 | 22555471 | The ability of the incretin agents (glucagon-like peptide 1 [GLP-1] agonists and dipeptidyl peptidase IV [DPP-4] inhibitors) to improve glycaemia with a low associated risk of hypoglycaemia, together with beneficial/neutral effects on body weight, offers a significant advantage for both patients and treating clinicians. |
| 1704 | 22555471 | In 1986 they first documented a reduced incretin effect in patients with type 2 diabetes (Diabetologia 29:46-52), and then in 1993 they demonstrated that, in patients with poorly controlled type 2 diabetes, a single exogenous infusion of an incretin (GLP-1) increased insulin levels in a glucose-dependent manner and normalised fasting hyperglycaemia (Diabetologia 36:741-744). |
| 1705 | 22555471 | In the ensuing 26 years, progress in the field of incretin hormones has resulted in a greater understanding of the relative roles of GLP-1 and glucose-dependent insulinotropic polypeptide secretion and activity in the pathogenesis of type 2 diabetes and the important recognition that native GLP-1 is quickly degraded by the ubiquitous protease DPP-4. |
| 1706 | 22555471 | This has led to the development of GLP-1 agonists that are resistant to degradation by DPP-4 and of selective inhibitors of DPP-4 activity as therapeutic agents. |
| 1707 | 22555471 | GLP-1 agonists (exenatide and liraglutide) and DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin and linagliptin) currently represent effective treatment options for patients with type 2 diabetes. |
| 1708 | 22555471 | Several additional agents are in the pipeline, including longer acting DPP-4-resistant GLP-1 agonists. |
| 1709 | 22555471 | The ability of the incretin agents (glucagon-like peptide 1 [GLP-1] agonists and dipeptidyl peptidase IV [DPP-4] inhibitors) to improve glycaemia with a low associated risk of hypoglycaemia, together with beneficial/neutral effects on body weight, offers a significant advantage for both patients and treating clinicians. |
| 1710 | 22555471 | In 1986 they first documented a reduced incretin effect in patients with type 2 diabetes (Diabetologia 29:46-52), and then in 1993 they demonstrated that, in patients with poorly controlled type 2 diabetes, a single exogenous infusion of an incretin (GLP-1) increased insulin levels in a glucose-dependent manner and normalised fasting hyperglycaemia (Diabetologia 36:741-744). |
| 1711 | 22555471 | In the ensuing 26 years, progress in the field of incretin hormones has resulted in a greater understanding of the relative roles of GLP-1 and glucose-dependent insulinotropic polypeptide secretion and activity in the pathogenesis of type 2 diabetes and the important recognition that native GLP-1 is quickly degraded by the ubiquitous protease DPP-4. |
| 1712 | 22555471 | This has led to the development of GLP-1 agonists that are resistant to degradation by DPP-4 and of selective inhibitors of DPP-4 activity as therapeutic agents. |
| 1713 | 22555471 | GLP-1 agonists (exenatide and liraglutide) and DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin and linagliptin) currently represent effective treatment options for patients with type 2 diabetes. |
| 1714 | 22555471 | Several additional agents are in the pipeline, including longer acting DPP-4-resistant GLP-1 agonists. |
| 1715 | 22555471 | The ability of the incretin agents (glucagon-like peptide 1 [GLP-1] agonists and dipeptidyl peptidase IV [DPP-4] inhibitors) to improve glycaemia with a low associated risk of hypoglycaemia, together with beneficial/neutral effects on body weight, offers a significant advantage for both patients and treating clinicians. |
| 1716 | 22555471 | In 1986 they first documented a reduced incretin effect in patients with type 2 diabetes (Diabetologia 29:46-52), and then in 1993 they demonstrated that, in patients with poorly controlled type 2 diabetes, a single exogenous infusion of an incretin (GLP-1) increased insulin levels in a glucose-dependent manner and normalised fasting hyperglycaemia (Diabetologia 36:741-744). |
| 1717 | 22555471 | In the ensuing 26 years, progress in the field of incretin hormones has resulted in a greater understanding of the relative roles of GLP-1 and glucose-dependent insulinotropic polypeptide secretion and activity in the pathogenesis of type 2 diabetes and the important recognition that native GLP-1 is quickly degraded by the ubiquitous protease DPP-4. |
| 1718 | 22555471 | This has led to the development of GLP-1 agonists that are resistant to degradation by DPP-4 and of selective inhibitors of DPP-4 activity as therapeutic agents. |
| 1719 | 22555471 | GLP-1 agonists (exenatide and liraglutide) and DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin and linagliptin) currently represent effective treatment options for patients with type 2 diabetes. |
| 1720 | 22555471 | Several additional agents are in the pipeline, including longer acting DPP-4-resistant GLP-1 agonists. |
| 1721 | 22555471 | The ability of the incretin agents (glucagon-like peptide 1 [GLP-1] agonists and dipeptidyl peptidase IV [DPP-4] inhibitors) to improve glycaemia with a low associated risk of hypoglycaemia, together with beneficial/neutral effects on body weight, offers a significant advantage for both patients and treating clinicians. |
| 1722 | 22555471 | In 1986 they first documented a reduced incretin effect in patients with type 2 diabetes (Diabetologia 29:46-52), and then in 1993 they demonstrated that, in patients with poorly controlled type 2 diabetes, a single exogenous infusion of an incretin (GLP-1) increased insulin levels in a glucose-dependent manner and normalised fasting hyperglycaemia (Diabetologia 36:741-744). |
| 1723 | 22555471 | In the ensuing 26 years, progress in the field of incretin hormones has resulted in a greater understanding of the relative roles of GLP-1 and glucose-dependent insulinotropic polypeptide secretion and activity in the pathogenesis of type 2 diabetes and the important recognition that native GLP-1 is quickly degraded by the ubiquitous protease DPP-4. |
| 1724 | 22555471 | This has led to the development of GLP-1 agonists that are resistant to degradation by DPP-4 and of selective inhibitors of DPP-4 activity as therapeutic agents. |
| 1725 | 22555471 | GLP-1 agonists (exenatide and liraglutide) and DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin and linagliptin) currently represent effective treatment options for patients with type 2 diabetes. |
| 1726 | 22555471 | Several additional agents are in the pipeline, including longer acting DPP-4-resistant GLP-1 agonists. |
| 1727 | 22555472 | In addition, a variety of glucose-lowering drugs including sulfonylureas, glinide-derivatives, and incretin-related drugs such as dipeptidyl peptidase IV (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists are used for glycaemic control by targeting beta cell signalling for improved insulin secretion. |
| 1728 | 22615074 | Incretin therapies, consisting of the injectable glucagon-like peptide-1 (GLP-1) receptor agonists and the oral dipeptidyl peptidase-4 (DPP-4) inhibitors, are a promising new class of antihyperglycemic drugs. |
| 1729 | 22621171 | Metformin appears to have the best benefit/risk ratio, and the dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists and analogues also appear promising, although these agents have not been specifically studied in populations with mood disorders. |
| 1730 | 22701182 | However, due to the rapid degradation of GLP-1 by dipeptidylpeptidase-IV (DPP-IV) enzyme and renal elimination of exendin-4, their clinical applications have been restricted. |
| 1731 | 22705459 | Exendin-4, glucagon-like peptide 1 (GLP-1) receptor agonist, is an exocrine hormone, which has potent insulinotropic actions similar to GLP-1 such as stimulating insulin biosynthesis, facilitating glucose concentration dependent insulin secretion, slowing gastric emptying, reducing food intake and stimulating β-cell proliferation. |
| 1732 | 22705459 | Exendin-4, also, has a longer half-life than GLP-1, due to its resistance to degradation by dipeptidyl peptidase-IV (DPP-IV). |
| 1733 | 22705459 | Increased expression of exendin-4, glucose dependent insulin secretion in NIT-1 insulinoma cells, and high insulin expression in the presence of DPP-IV were evaluated in vitro after delivery of ABP/TSTA-SP-exendin-4. |
| 1734 | 22705459 | Exendin-4, glucagon-like peptide 1 (GLP-1) receptor agonist, is an exocrine hormone, which has potent insulinotropic actions similar to GLP-1 such as stimulating insulin biosynthesis, facilitating glucose concentration dependent insulin secretion, slowing gastric emptying, reducing food intake and stimulating β-cell proliferation. |
| 1735 | 22705459 | Exendin-4, also, has a longer half-life than GLP-1, due to its resistance to degradation by dipeptidyl peptidase-IV (DPP-IV). |
| 1736 | 22705459 | Increased expression of exendin-4, glucose dependent insulin secretion in NIT-1 insulinoma cells, and high insulin expression in the presence of DPP-IV were evaluated in vitro after delivery of ABP/TSTA-SP-exendin-4. |
| 1737 | 22718884 | Dipeptidyl peptidase 4 (DPP4) is an exopeptidase which modulates the function of its substrates, among which are insulin-releasing incretins. |
| 1738 | 22718884 | VG did not affect regeneration but decreased apoptosis, as shown by twofold decreased Bax/Bcl-2 mRNA expression and a threefold decrease in apoptotic bodies on terminal deoxynucleotidyl transferase dUTP nick-end labeling-stained sections. |
| 1739 | 22761607 | Novel incretin-based drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i), have been last introduced in the pharmacological treatment of type 2 diabetes. |
| 1740 | 22804102 | We conclude that metformin may prove useful in macrovascular disease reduction, while pramlintide, glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors and leptin co-therapies may reduce HbA(1c) , glucose variability, postprandial glucose excursions and body weight. |
| 1741 | 22804249 | In this study, we investigated the effects of linagliptin (a DPP-4 inhibitor) and BI-38335 (an SGLT2 inhibitor), individually and in combination, on glucose homeostasis, islet function, and pancreatic islet morphology in db/db mice. |
| 1742 | 22804249 | Active treatments markedly reduced blood glucose and glycated hemoglobin A1c (HbA(1c)) levels, with the combined treatment showing the greater effects. |
| 1743 | 22804249 | Insulin resistance was improved in the BI-38335 and combination groups with the enhancement of insulin sensitivity and significant increase of serum adiponectin levels. |
| 1744 | 22822047 | Vildagliptin, a dipeptidyl peptidase 4 inhibitor, is representative of a new class of antidiabetic agents that act through increasing the expression of glucagon-like peptide-1. |
| 1745 | 22832924 | Natriuretic effect by exendin-4, but not the DPP-4 inhibitor alogliptin, is mediated via the GLP-1 receptor and preserved in obese type 2 diabetic mice. |
| 1746 | 22832924 | Activation of the glucagon-like peptide (GLP)-1 receptor (GLP-1R) and inhibition of dipeptidyl peptidase-4 (DPP-4) are new antidiabetic strategies. |
| 1747 | 22832924 | The GLP-1R and DPP-4 are also expressed in the renal proximal tubular brush border, where they may regulate Na(+) reabsorption. |
| 1748 | 22832924 | DPP-4 cleaves and inactivates GLP-1; thus the natriuretic effect of DPP-4 inhibition may be mediated by the GLP-1R. |
| 1749 | 22832924 | These effects were absent in mice lacking the GLP-1R and independent of adenylyl cyclase 6. |
| 1750 | 22832924 | In comparison, parenteral application of the DPP-4 inhibitor alogliptin reduced plasma DPP-4 activity by 95% and induced a diuresis and natriuresis independent of the presence of the GLP-1R or changes in phosphorylated NHE3. |
| 1751 | 22832924 | Natriuretic effect by exendin-4, but not the DPP-4 inhibitor alogliptin, is mediated via the GLP-1 receptor and preserved in obese type 2 diabetic mice. |
| 1752 | 22832924 | Activation of the glucagon-like peptide (GLP)-1 receptor (GLP-1R) and inhibition of dipeptidyl peptidase-4 (DPP-4) are new antidiabetic strategies. |
| 1753 | 22832924 | The GLP-1R and DPP-4 are also expressed in the renal proximal tubular brush border, where they may regulate Na(+) reabsorption. |
| 1754 | 22832924 | DPP-4 cleaves and inactivates GLP-1; thus the natriuretic effect of DPP-4 inhibition may be mediated by the GLP-1R. |
| 1755 | 22832924 | These effects were absent in mice lacking the GLP-1R and independent of adenylyl cyclase 6. |
| 1756 | 22832924 | In comparison, parenteral application of the DPP-4 inhibitor alogliptin reduced plasma DPP-4 activity by 95% and induced a diuresis and natriuresis independent of the presence of the GLP-1R or changes in phosphorylated NHE3. |
| 1757 | 22832924 | Natriuretic effect by exendin-4, but not the DPP-4 inhibitor alogliptin, is mediated via the GLP-1 receptor and preserved in obese type 2 diabetic mice. |
| 1758 | 22832924 | Activation of the glucagon-like peptide (GLP)-1 receptor (GLP-1R) and inhibition of dipeptidyl peptidase-4 (DPP-4) are new antidiabetic strategies. |
| 1759 | 22832924 | The GLP-1R and DPP-4 are also expressed in the renal proximal tubular brush border, where they may regulate Na(+) reabsorption. |
| 1760 | 22832924 | DPP-4 cleaves and inactivates GLP-1; thus the natriuretic effect of DPP-4 inhibition may be mediated by the GLP-1R. |
| 1761 | 22832924 | These effects were absent in mice lacking the GLP-1R and independent of adenylyl cyclase 6. |
| 1762 | 22832924 | In comparison, parenteral application of the DPP-4 inhibitor alogliptin reduced plasma DPP-4 activity by 95% and induced a diuresis and natriuresis independent of the presence of the GLP-1R or changes in phosphorylated NHE3. |
| 1763 | 22832924 | Natriuretic effect by exendin-4, but not the DPP-4 inhibitor alogliptin, is mediated via the GLP-1 receptor and preserved in obese type 2 diabetic mice. |
| 1764 | 22832924 | Activation of the glucagon-like peptide (GLP)-1 receptor (GLP-1R) and inhibition of dipeptidyl peptidase-4 (DPP-4) are new antidiabetic strategies. |
| 1765 | 22832924 | The GLP-1R and DPP-4 are also expressed in the renal proximal tubular brush border, where they may regulate Na(+) reabsorption. |
| 1766 | 22832924 | DPP-4 cleaves and inactivates GLP-1; thus the natriuretic effect of DPP-4 inhibition may be mediated by the GLP-1R. |
| 1767 | 22832924 | These effects were absent in mice lacking the GLP-1R and independent of adenylyl cyclase 6. |
| 1768 | 22832924 | In comparison, parenteral application of the DPP-4 inhibitor alogliptin reduced plasma DPP-4 activity by 95% and induced a diuresis and natriuresis independent of the presence of the GLP-1R or changes in phosphorylated NHE3. |
| 1769 | 22832924 | Natriuretic effect by exendin-4, but not the DPP-4 inhibitor alogliptin, is mediated via the GLP-1 receptor and preserved in obese type 2 diabetic mice. |
| 1770 | 22832924 | Activation of the glucagon-like peptide (GLP)-1 receptor (GLP-1R) and inhibition of dipeptidyl peptidase-4 (DPP-4) are new antidiabetic strategies. |
| 1771 | 22832924 | The GLP-1R and DPP-4 are also expressed in the renal proximal tubular brush border, where they may regulate Na(+) reabsorption. |
| 1772 | 22832924 | DPP-4 cleaves and inactivates GLP-1; thus the natriuretic effect of DPP-4 inhibition may be mediated by the GLP-1R. |
| 1773 | 22832924 | These effects were absent in mice lacking the GLP-1R and independent of adenylyl cyclase 6. |
| 1774 | 22832924 | In comparison, parenteral application of the DPP-4 inhibitor alogliptin reduced plasma DPP-4 activity by 95% and induced a diuresis and natriuresis independent of the presence of the GLP-1R or changes in phosphorylated NHE3. |
| 1775 | 22868389 | Dipeptidyl peptidase 4 inhibitor sitagliptin protects endothelial function in hypertension through a glucagon-like peptide 1-dependent mechanism. |
| 1776 | 22868389 | Sitagliptin, a selective dipeptidyl peptidase 4 inhibitor, inhibits the inactivation and degradation of glucagon like peptide 1 (GLP-1), which is used for the treatment of type 2 diabetes mellitus. |
| 1777 | 22868389 | In vivo sitagliptin treatment elevated GLP-1 and GLP-1 receptor expressions, increased cAMP level, and subsequently activated protein kinase A, liver kinase B1, AMP-activated protein kinase-α and endothelial NO synthase in spontaneously hypertensive rat renal arteries. |
| 1778 | 22868389 | Inhibition of GLP-1 receptor, adenylyl cyclase, protein kinase A, AMP-activated protein kinase-α, or NO synthase reversed the protective effects of sitagliptin. |
| 1779 | 22868389 | Studies using transient expressions of wild-type and dominant-negative AMP-activated protein kinase-α2 support the critical role of AMP-activated protein kinase-α in mediating the effect of GLP-1 in endothelial cells. |
| 1780 | 22868389 | Dipeptidyl peptidase 4 inhibitor sitagliptin protects endothelial function in hypertension through a glucagon-like peptide 1-dependent mechanism. |
| 1781 | 22868389 | Sitagliptin, a selective dipeptidyl peptidase 4 inhibitor, inhibits the inactivation and degradation of glucagon like peptide 1 (GLP-1), which is used for the treatment of type 2 diabetes mellitus. |
| 1782 | 22868389 | In vivo sitagliptin treatment elevated GLP-1 and GLP-1 receptor expressions, increased cAMP level, and subsequently activated protein kinase A, liver kinase B1, AMP-activated protein kinase-α and endothelial NO synthase in spontaneously hypertensive rat renal arteries. |
| 1783 | 22868389 | Inhibition of GLP-1 receptor, adenylyl cyclase, protein kinase A, AMP-activated protein kinase-α, or NO synthase reversed the protective effects of sitagliptin. |
| 1784 | 22868389 | Studies using transient expressions of wild-type and dominant-negative AMP-activated protein kinase-α2 support the critical role of AMP-activated protein kinase-α in mediating the effect of GLP-1 in endothelial cells. |
| 1785 | 22915295 | Pharmacological treatment with sitagliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor, also reduces glycemia by increasing glucagon-like peptide-1 (GLP-1). |
| 1786 | 22948814 | In this study, we combined the dipeptidyl peptidase-4 inhibitor sitagliptin with the antidiabetic drug mangiferin to examine the effects on active glucagon-like peptide-1 (GLP-1) and glucose tolerance in streptozotocin-diabetic rats. |
| 1787 | 22948814 | In addition, the combination therapy improved glucose tolerance with an increase in plasma insulin level and active GLP-1 levels. |
| 1788 | 22973260 | Glucagon-like peptide-1 (GLP-1) is an incretin hormone responsible for amplification of insulin secretion when nutrients are given orally as opposed to intravenously and it retains its insulinotropic activity in patients with type 2 diabetes mellitus (T2D). |
| 1789 | 22973260 | GLP-1 based therapies, such as GLP-1 receptor (GLP-1R) agonists and inhibitors of dipeptidyl peptidase-4, an enzyme that degrades endogenous GLP-1 are routinely used to treat patients with T2D. |
| 1790 | 22994702 | Among these, compounds 7j, 7q, and 7s displayed good dipeptidyl peptidase-4 activity and excellent selectivity versus other proteases including dipeptidyl peptidase-8, dipeptidyl peptidase-9, and FAP. |
| 1791 | 23011352 | Treatment of autoimmune diabetes in NOD mice by Toll-like receptor 2 tolerance in conjunction with dipeptidyl peptidase 4 inhibition. |
| 1792 | 23060974 | In addition to the conventional therapy for DM, glucagon-like peptide-1 (GLP-1) mimetics, dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinediones (TZDs), and insulin analogues are currently available effective hypoglycemic agents for the management of the patients with DM in the perioperative period and also consider the adverse effects of newly introduced agents that need more clinical observations. |
| 1793 | 23066003 | Treatment of a life-threatening laryngeal bradykinin angio-oedema precipitated by dipeptidylpeptidase-4 inhibitor and angiotensin-I converting enzyme inhibitor with prothrombin complex concentrates. |
| 1794 | 23071636 | Attenuation of renovascular damage in Zucker diabetic fatty rat by NWT-03, an egg protein hydrolysate with ACE- and DPP4-inhibitory Activity. |
| 1795 | 23094100 | Glucagon-like peptide-1 (GLP-1) released from intestinal L cells in response to nutrients has many physiological effects but particularly enhances glucose-dependent insulin release through the GLP-1 receptor (GLP-1R). |
| 1796 | 23094100 | GLP-1 7-36 amide, the predominant circulating active form of GLP-1, is rapidly truncated by dipeptidyl peptidase-4 to GLP-1 9-36 amide, which is generally considered inactive. |
| 1797 | 23094100 | Recently 'compound 2' has been described as both an agonist and positive allosteric modulator of GLP-1 7-36 amide affinity, but not potency, at the GLP-1R. |
| 1798 | 23094100 | Given that GLP-1 9-36 amide is the major circulating form of GLP-1 post-prandially and is a low affinity weak partial agonist or antagonist at the GLP-1R, we investigated interaction between this metabolite and compound 2 in a cell line with recombinant expression of the human GLP-1R and the rat insulinoma cell line, INS-1E, with native expression of the GLP-1R. |
| 1799 | 23094100 | We show compound 2 markedly enhances efficacy and potency of GLP-1 9-36 amide for key cellular responses including AMP generation, Ca(2+) signaling and extracellular signal-regulated kinase. |
| 1800 | 23184939 | Dipeptidyl peptidase IV (DPP-IV) degrades the incretin hormone glucagon-like peptide 1 (GLP-1). |
| 1801 | 23197976 | Because experimental and pathological studies suggest that incretin hormone glucagon-like peptide-1 may improves VEGF generation and promote the upregulation of HIF-1α through a reduction of oxidative stress, the study evaluated the effect of the augmentation of GLP-1, by inhibitors of the dipeptidyl peptidase-4, such as vildagliptin, on angiogenesis process and wound healing in diabetic chronic ulcers. |
| 1802 | 23209191 | Blood DPP-4 activity, glucagon-like peptide-1 (GLP-1) levels, glucose, body weight, and food intake were assessed throughout the experiments. |
| 1803 | 23212669 | Newer drugs that may improve the currently very limited treatment options for patients with type 2 diabetes and renal impairment include the glucagon-like peptide-1 receptor agonists and the dipeptidyl peptidase-4 inhibitors. |
| 1804 | 23219487 | Trp-Val and one lactoferrin hydrolysate (LFH1) were multifunctional displaying both DPP-IV inhibitory and antioxidant (SO and DPPH scavenging) activities. |
| 1805 | 23241684 | Novel adipokines secreted from adipocytes such as retinol binding protein-4 (RBP-4), vaspin, omentin, chemerin, fibroblast growth factor 21 (FGF21), adipocyte fatty acid-binding protein (A-FABP) and dipeptidyl peptidase 4 (DPP4) demonstrate pleiotropic activity and their insulin-sensitizing or enhancing insulin resistance properties have not been clearly confirmed yet. |
| 1806 | 23258123 | The assessment of the effects on cardiovascular risk is necessary for all new drugs for diabetes, including glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. |
| 1807 | 23258123 | Meta-analyses of the same trials, combining all molecules of each class, showed that DPP-4 inhibitors are associated with a significant reduction of major cardiovascular events and mortality; in trials with GLP-1 receptor agonists, which are fewer because of the smaller number of available molecules, a similar trend is observed, reaching statistical significance only for major cardiovascular events in placebo-controlled trials. |
| 1808 | 23258123 | The assessment of the effects on cardiovascular risk is necessary for all new drugs for diabetes, including glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. |
| 1809 | 23258123 | Meta-analyses of the same trials, combining all molecules of each class, showed that DPP-4 inhibitors are associated with a significant reduction of major cardiovascular events and mortality; in trials with GLP-1 receptor agonists, which are fewer because of the smaller number of available molecules, a similar trend is observed, reaching statistical significance only for major cardiovascular events in placebo-controlled trials. |
| 1810 | 23304532 | Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1) inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. |
| 1811 | 23304532 | Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors) is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain. |
| 1812 | 23319869 | DPP-4 inhibitors act by increasing endogenous GLP-1 and GIP concentrations. |
| 1813 | 23345558 | The GLP-2 increases bicarbonate secretion via release of vasoactive intestinal peptide (VIP) from myenteric nerves. |
| 1814 | 23345558 | The GLP are metabolized by dipeptidyl peptidase IV (DPPIV), an enzyme of particular interest to pharmaceutical, because its inhibition increases plasma concentrations of GLP-1 to treat diabetes. |
| 1815 | 23345558 | We have also reported that DPPIV inhibition enhances the secretory effects of nutrient-evoked GLP-2. |
| 1816 | 23345558 | The GLP-2 increases bicarbonate secretion via release of vasoactive intestinal peptide (VIP) from myenteric nerves. |
| 1817 | 23345558 | The GLP are metabolized by dipeptidyl peptidase IV (DPPIV), an enzyme of particular interest to pharmaceutical, because its inhibition increases plasma concentrations of GLP-1 to treat diabetes. |
| 1818 | 23345558 | We have also reported that DPPIV inhibition enhances the secretory effects of nutrient-evoked GLP-2. |
| 1819 | 23358258 | Compounds H4 and H9 showed good DPP-4 inhibition and more than 100-fold selectivity over DPP-7 and DPP-8. |
| 1820 | 23364453 | Cohorts of diabetic rats received a 12-week treatment of vildagliptin (dipeptidyl peptidase-4 inhibitor) or exenatide (GLP-1 analog). |
| 1821 | 23364453 | GLP-1 decreased high-glucose-induced reactive oxygen species production and apoptotic index, as well as the levels of NADPH oxidase such as p47(phox) and gp91(phox). |
| 1822 | 23364453 | Furthermore, cAMP/PKA (cAMP-dependent protein kinase activity) was increased and Rho-expression was decreased in high-glucose-induced CMECs after GLP-1 treatment. |
| 1823 | 23444823 | Finally, inhibitors of dipeptidyl peptidase-4 (glitpins), by inhibiting glucagon secretion, and inhibitors of renal SGLT2 cotransporters, thus promoting glucosuria independently of insulin, might also be beneficial in type 1 diabetes, although specific studies are still ongoing to verify this hypothesis. |
| 1824 | 23446787 | Available oral antidiabetic drugs include insulin secretagogues (meglitinides and sulfonylureas), biguanides (metformin), α-glucosidase inhibitors, thiazolidinediones and inhibitors of glucagon-like peptide 1 (GLP-1) degrading enzyme dipeptidyl peptidase 4. |
| 1825 | 23459193 | These agents could be divided into 2 main groups, glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 inhibitors. |
| 1826 | 23459193 | Endogenous GLP-1 is an incretin hormone composed by a 30-amino acid peptide and is secreted from L-cells in distal small intestine in response to calorie intake, causing a glucose-dependent β-cell response resulting in a restoration of the first-phase insulin response. |
| 1827 | 23479200 | The place of GLP-1-based therapy in diabetes management: differences between DPP-4 inhibitors and GLP-1 receptor agonists. |
| 1828 | 23489968 | The present short review summarizes and updates clinical experience with two classes of drugs introduced for the management of type 2 diabetes mellitus over the past 8 years: (i) the glucagon-like peptide-1 receptor agonists; and (ii) the dipeptidyl peptidase 4 inhibitors. |
| 1829 | 23504176 | As dipeptidyl-peptidase IV (DPP-IV) inhibition increases plasma GLP-1 levels in vivo, we investigated the cardioprotective effects of the DPP-IV inhibitor vildagliptin in a murine heart failure (HF) model. |
| 1830 | 23512382 | Reshaping diabetes care: the fundamental role of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists in clinical practice. |
| 1831 | 23522180 | Incretins (gastric inhibitory polypeptide and glucagon-like peptide 1 [GLP-1]) are hormones released from the gastrointestinal tract during food intake that potentiate insulin secretion. |
| 1832 | 23522180 | Native GLP-1 is quickly degraded by the enzyme dipeptidylpeptidase-4 (DPP-4), which has led to the development of GLP-1 agonists with resistance to degradation and to inhibitors of DPP-4 activity as therapeutic agents in humans with type 2 diabetes. |
| 1833 | 23522180 | In healthy cats, GLP-1 agonists and DPP-4 inhibitors have produced a substantial increase in insulin secretion. |
| 1834 | 23523140 | The pharmacological features distinguishing GLP-1 receptor agonists from DPP-4 inhibitors are discussed here to address their respective positions in type 2 diabetes. |
| 1835 | 23523479 | Antipsychotic-like effect of GLP-1 agonist liraglutide but not DPP-IV inhibitor sitagliptin in mouse model for psychosis. |
| 1836 | 23523479 | GLP-1 agonist (liraglutide) and dipeptidyl peptidase-IV (DPP-IV) inhibitor (sitagliptin) are the US-FDA approved medications for the management of T2DM. |
| 1837 | 23523479 | Antipsychotic-like effect of GLP-1 agonist liraglutide but not DPP-IV inhibitor sitagliptin in mouse model for psychosis. |
| 1838 | 23523479 | GLP-1 agonist (liraglutide) and dipeptidyl peptidase-IV (DPP-IV) inhibitor (sitagliptin) are the US-FDA approved medications for the management of T2DM. |
| 1839 | 23564338 | Mechanistic studies in healthy volunteers suggest that pasireotide-associated hyperglycemia is due to reduced secretion of glucagon-like peptide (GLP)-1, glucose-dependent insulinotropic polypeptide, and insulin; however, it is associated with intact postprandial glucagon secretion. |
| 1840 | 23564338 | Diabetes mellitus should be managed by initiation of medical therapy with metformin and staged treatment intensification with a dipeptidyl peptidase-4 inhibitor, with a switch to a GLP-1 receptor agonist and initiation of insulin, as required, to achieve and maintain glycemic control. |
| 1841 | 23570814 | GLP-1 receptor agonists or DPP-4 inhibitors: how to guide the clinician? |
| 1842 | 23570814 | Such medications comprise either GLP-1 receptor agonists, with short (one or two daily injections: exenatide, liraglutide, lixisenatide) or long duration (one injection once weekly: extended-released exenatide, albiglutide, dulaglutide, taspoglutide); or oral compounds inhibiting dipeptidyl peptidase-4 (DPP-4), the enzyme that inactives GLP-1, also called gliptins (sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin). |
| 1843 | 23570814 | Gliptins may represent a valuable alternative to a sulfonylurea or a glitazone after failure of monotherapy with metformin while GLP-1 receptor agonists may be considered as a good alternative to insulin (especially in obese patients) after failure of a dual oral therapy. |
| 1844 | 23570814 | GLP-1 receptor agonists or DPP-4 inhibitors: how to guide the clinician? |
| 1845 | 23570814 | Such medications comprise either GLP-1 receptor agonists, with short (one or two daily injections: exenatide, liraglutide, lixisenatide) or long duration (one injection once weekly: extended-released exenatide, albiglutide, dulaglutide, taspoglutide); or oral compounds inhibiting dipeptidyl peptidase-4 (DPP-4), the enzyme that inactives GLP-1, also called gliptins (sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin). |
| 1846 | 23570814 | Gliptins may represent a valuable alternative to a sulfonylurea or a glitazone after failure of monotherapy with metformin while GLP-1 receptor agonists may be considered as a good alternative to insulin (especially in obese patients) after failure of a dual oral therapy. |
| 1847 | 23586735 | Potential for cardiac protection with dipeptidyl peptidase-4 inhibitors: the stromal cell-derived factor-1α hypothesis. |
| 1848 | 23591914 | DPP-4 inhibitors improve cognition and brain mitochondrial function of insulin-resistant rats. |
| 1849 | 23591914 | Our findings suggest that the inhibition of dipeptidyl-peptidase-4 enzymes with vildagliptin or sitagliptin in insulin-resistant rats not only increases peripheral insulin sensitivity but also decreases brain dysfunction. |
| 1850 | 23591914 | DPP-4 inhibitors improve cognition and brain mitochondrial function of insulin-resistant rats. |
| 1851 | 23591914 | Our findings suggest that the inhibition of dipeptidyl-peptidase-4 enzymes with vildagliptin or sitagliptin in insulin-resistant rats not only increases peripheral insulin sensitivity but also decreases brain dysfunction. |
| 1852 | 23599045 | Rapid degradation of glucagon-like peptide-1 (GLP-1) by dipeptidyl peptidase-4 suggests that endogenous GLP-1 may act locally before being degraded. |
| 1853 | 23599045 | Insulin secretion was unaffected by exogenous GLP-1 in vagotomized subjects but was suppressed in controls. |
| 1854 | 23599045 | Our results demonstrate that vagotomy with pyloroplasty impairs the effects of exogenous GLP-1 on food intake, gastric emptying, and insulin and glucagon secretion, suggesting that intact vagal innervation may be important for GLP-1's actions. |
| 1855 | 23602966 | Glucagon-like peptide-1 (GLP-1), an enhancer of insulin production with a trophic effect on β cells in the islets, has been found to be trophic for neuronal cells. |
| 1856 | 23602966 | Alogliptin benzoate (AGL), a selective inhibitor of dipeptidylpeptidase-4 (DPP-4) functioning as a long-acting agonist of GLP-1, is in clinical use worldwide for patients with diabetes mellitus type 2. |
| 1857 | 23603201 | Pharmacological agents, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, which increase the level of glucagon-like peptide-1 (GLP-1) and ameliorate T2D, have become valuable candidates as disease modifying agents in the treatment of AD. |
| 1858 | 23603201 | In addition, endogenous GLP-1 levels decrease amyloid beta (Aβ) peptide and tau phosphorylation in AD. |
| 1859 | 23603201 | The effect of the DPP-4 inhibitor on hippocampal GLP-1 levels, Aβ burden, tau phosphorylation, inflammatory markers and memory retention were evaluated. |
| 1860 | 23603201 | The results reveal an attenuation of Aβ, tau phosphorylation and inflammatory markers and an improvement in hippocampal GLP-1 and memory retention following treatment. |
| 1861 | 23603201 | This remarkable therapeutic effect of Saxagliptin mediated through DPP-4 inhibition demonstrates a unique mechanism for Aβ and tau clearance by increasing GLP-1 levels and reverses the behavioural deficits and pathology observed in AD. |
| 1862 | 23603201 | Pharmacological agents, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, which increase the level of glucagon-like peptide-1 (GLP-1) and ameliorate T2D, have become valuable candidates as disease modifying agents in the treatment of AD. |
| 1863 | 23603201 | In addition, endogenous GLP-1 levels decrease amyloid beta (Aβ) peptide and tau phosphorylation in AD. |
| 1864 | 23603201 | The effect of the DPP-4 inhibitor on hippocampal GLP-1 levels, Aβ burden, tau phosphorylation, inflammatory markers and memory retention were evaluated. |
| 1865 | 23603201 | The results reveal an attenuation of Aβ, tau phosphorylation and inflammatory markers and an improvement in hippocampal GLP-1 and memory retention following treatment. |
| 1866 | 23603201 | This remarkable therapeutic effect of Saxagliptin mediated through DPP-4 inhibition demonstrates a unique mechanism for Aβ and tau clearance by increasing GLP-1 levels and reverses the behavioural deficits and pathology observed in AD. |
| 1867 | 23603201 | Pharmacological agents, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, which increase the level of glucagon-like peptide-1 (GLP-1) and ameliorate T2D, have become valuable candidates as disease modifying agents in the treatment of AD. |
| 1868 | 23603201 | In addition, endogenous GLP-1 levels decrease amyloid beta (Aβ) peptide and tau phosphorylation in AD. |
| 1869 | 23603201 | The effect of the DPP-4 inhibitor on hippocampal GLP-1 levels, Aβ burden, tau phosphorylation, inflammatory markers and memory retention were evaluated. |
| 1870 | 23603201 | The results reveal an attenuation of Aβ, tau phosphorylation and inflammatory markers and an improvement in hippocampal GLP-1 and memory retention following treatment. |
| 1871 | 23603201 | This remarkable therapeutic effect of Saxagliptin mediated through DPP-4 inhibition demonstrates a unique mechanism for Aβ and tau clearance by increasing GLP-1 levels and reverses the behavioural deficits and pathology observed in AD. |
| 1872 | 23631252 | [Significance of combination therapy with an insulin sensitizer and a DPP-4(dipeptidyl peptidase-4) inhibitor]. |
| 1873 | 23631252 | Insulin sensitizers such as metformin and pioglitazone reduce peripheral insulin resistance, whereas dipeptidyl peptidase-4(DPP-4) inhibitors augment postprandial insulin secretion and inhibit glucagon secretion. |
| 1874 | 23631252 | Combination therapy with an insulin sensitizer and a DPP-4 inhibitor provides substantial and additive glycemic improvement because of the complementary mechanisms of action of these agents. |
| 1875 | 23631252 | [Significance of combination therapy with an insulin sensitizer and a DPP-4(dipeptidyl peptidase-4) inhibitor]. |
| 1876 | 23631252 | Insulin sensitizers such as metformin and pioglitazone reduce peripheral insulin resistance, whereas dipeptidyl peptidase-4(DPP-4) inhibitors augment postprandial insulin secretion and inhibit glucagon secretion. |
| 1877 | 23631252 | Combination therapy with an insulin sensitizer and a DPP-4 inhibitor provides substantial and additive glycemic improvement because of the complementary mechanisms of action of these agents. |
| 1878 | 23631252 | [Significance of combination therapy with an insulin sensitizer and a DPP-4(dipeptidyl peptidase-4) inhibitor]. |
| 1879 | 23631252 | Insulin sensitizers such as metformin and pioglitazone reduce peripheral insulin resistance, whereas dipeptidyl peptidase-4(DPP-4) inhibitors augment postprandial insulin secretion and inhibit glucagon secretion. |
| 1880 | 23631252 | Combination therapy with an insulin sensitizer and a DPP-4 inhibitor provides substantial and additive glycemic improvement because of the complementary mechanisms of action of these agents. |
| 1881 | 23632200 | However, the therapeutic potential of endogenous GLP-1 is limited, because of rapid inactivation by dipeptidyl peptidase-4. |
| 1882 | 23637948 | In this study, we validated the regulation and release of two selected myokines, namely pigment epithelium derived factor (PEDF) and dipeptidyl peptidase 4 (DPP4), which were recently described as adipokines. |
| 1883 | 23637948 | This study reveals that both factors, DPP4 and PEDF, are secreted by primary human myotubes. |
| 1884 | 23637948 | In this study, we validated the regulation and release of two selected myokines, namely pigment epithelium derived factor (PEDF) and dipeptidyl peptidase 4 (DPP4), which were recently described as adipokines. |
| 1885 | 23637948 | This study reveals that both factors, DPP4 and PEDF, are secreted by primary human myotubes. |
| 1886 | 23643015 | It had been proposed that DPP-4 inhibitors exert their antidiabetic effect by inhibiting the degradation of glucagon-like peptide 1(GLP-1) . |
| 1887 | 23643015 | In recent years, studies have revealed many possible mechanisms through which DPP-4 inhibitors regulate glycemia: DPP-4 inhibitors may selectively reduce DPP-4 activity in the intestine, causing the increase of portal plasma GLP-1 level and thus promoting the release of insulin via nerve reflex;also, they may decrease the cleavage product of GLP-1 and reduce the degradation of other bioactive peptides. |
| 1888 | 23643015 | It had been proposed that DPP-4 inhibitors exert their antidiabetic effect by inhibiting the degradation of glucagon-like peptide 1(GLP-1) . |
| 1889 | 23643015 | In recent years, studies have revealed many possible mechanisms through which DPP-4 inhibitors regulate glycemia: DPP-4 inhibitors may selectively reduce DPP-4 activity in the intestine, causing the increase of portal plasma GLP-1 level and thus promoting the release of insulin via nerve reflex;also, they may decrease the cleavage product of GLP-1 and reduce the degradation of other bioactive peptides. |
| 1890 | 23643052 | The dipeptidyl peptidase-4 (DPP-4) ectopeptidase cleaves several proteins, including the incretin hormones that regulate meal-induced insulin release. |
| 1891 | 23645229 | Dipeptidyl peptidase-4 (DPP-4 or CD26) inhibitors, a new class of oral anti-hyperglycemic agents that prolong the bioavailability of the endogenously secreted incretin hormone glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic polypeptide (GIP), are effective in the treatment of diabetes. |
| 1892 | 23653460 | Pharmacological inhibition of dipeptidylpeptidase-4 (DPP-4) to increase the bioavailability of glucagon-like peptide-1 is an emerging therapy for control of glycemia in type 2 diabetes patients. |
| 1893 | 23653460 | Accumulating evidence suggests that glucagon-like peptide-1 has insulin-independent actions in cardiovascular tissue. |
| 1894 | 23668534 | Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel oral hypoglycaemic agents that protect glucagon-like peptide-1 (GLP-1) from degradation, maintain the bioactivity of endogenous GLP-1, and thus improve islet dysfunction. |
| 1895 | 23668534 | Moreover, recent studies have suggested that metformin enhances the biological effect of GLP-1 by increasing GLP-1 secretion, suppressing activity of DPP-4 and upregulating the expression of GLP-1 receptor in pancreatic β-cells. |
| 1896 | 23668534 | Conversely, DPP-4 inhibitors have a favourable effect on insulin sensitivity in patients with T2DM. |
| 1897 | 23668534 | Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel oral hypoglycaemic agents that protect glucagon-like peptide-1 (GLP-1) from degradation, maintain the bioactivity of endogenous GLP-1, and thus improve islet dysfunction. |
| 1898 | 23668534 | Moreover, recent studies have suggested that metformin enhances the biological effect of GLP-1 by increasing GLP-1 secretion, suppressing activity of DPP-4 and upregulating the expression of GLP-1 receptor in pancreatic β-cells. |
| 1899 | 23668534 | Conversely, DPP-4 inhibitors have a favourable effect on insulin sensitivity in patients with T2DM. |
| 1900 | 23668534 | Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel oral hypoglycaemic agents that protect glucagon-like peptide-1 (GLP-1) from degradation, maintain the bioactivity of endogenous GLP-1, and thus improve islet dysfunction. |
| 1901 | 23668534 | Moreover, recent studies have suggested that metformin enhances the biological effect of GLP-1 by increasing GLP-1 secretion, suppressing activity of DPP-4 and upregulating the expression of GLP-1 receptor in pancreatic β-cells. |
| 1902 | 23668534 | Conversely, DPP-4 inhibitors have a favourable effect on insulin sensitivity in patients with T2DM. |
| 1903 | 23674605 | GLP-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, which inhibit the physiological inactivation of endogenous GLP-1, are used for the treatment of type 2 diabetes. |
| 1904 | 23674605 | Using the Metabochip, we identified three novel genetic loci with large effects (30-40%) on GLP-1-stimulated insulin secretion during hyperglycemic clamps in nondiabetic Caucasian individuals (TMEM114; CHST3 and CTRB1/2; n = 232; all P ≤ 8.8 × 10(-7)). rs7202877 near CTRB1/2, a known diabetes risk locus, also associated with an absolute 0.51 ± 0.16% (5.6 ± 1.7 mmol/mol) lower A1C response to DPP-4 inhibitor treatment in G-allele carriers, but there was no effect on GLP-1 RA treatment in type 2 diabetic patients (n = 527). |
| 1905 | 23674605 | Furthermore, in pancreatic tissue, we show that rs7202877 acts as expression quantitative trait locus for CTRB1 and CTRB2, encoding chymotrypsinogen, and increases fecal chymotrypsin activity in healthy carriers. |
| 1906 | 23674605 | GLP-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, which inhibit the physiological inactivation of endogenous GLP-1, are used for the treatment of type 2 diabetes. |
| 1907 | 23674605 | Using the Metabochip, we identified three novel genetic loci with large effects (30-40%) on GLP-1-stimulated insulin secretion during hyperglycemic clamps in nondiabetic Caucasian individuals (TMEM114; CHST3 and CTRB1/2; n = 232; all P ≤ 8.8 × 10(-7)). rs7202877 near CTRB1/2, a known diabetes risk locus, also associated with an absolute 0.51 ± 0.16% (5.6 ± 1.7 mmol/mol) lower A1C response to DPP-4 inhibitor treatment in G-allele carriers, but there was no effect on GLP-1 RA treatment in type 2 diabetic patients (n = 527). |
| 1908 | 23674605 | Furthermore, in pancreatic tissue, we show that rs7202877 acts as expression quantitative trait locus for CTRB1 and CTRB2, encoding chymotrypsinogen, and increases fecal chymotrypsin activity in healthy carriers. |
| 1909 | 23680741 | Combination therapy with DPP-4 inhibitors and insulin in patients with type 2 diabetes mellitus: what is the evidence? |
| 1910 | 23680741 | In addition to the expected benefits associated with limiting insulin dose and regimen complexity, the specific advantages the DPP-4 inhibitor drug class on hypoglycemia and weight gain could justify combining DPP-4 inhibitors with insulin; additionally, a DPP-4 inhibitor may be of special value to decrease glycemic excursions that are not properly addressed by basal insulin therapy and metformin use, even after optimizing titration of the basal insulin. |
| 1911 | 23680741 | However, given the common original perception that treatment with DPP-4 inhibitors may be less beneficial with increasing disease progression because of the loss of β-cell function, the potential relevance of these agents in the setting of advanced T2DM treated with insulin was not necessarily anticipated. |
| 1912 | 23680741 | Combination therapy with DPP-4 inhibitors and insulin in patients with type 2 diabetes mellitus: what is the evidence? |
| 1913 | 23680741 | In addition to the expected benefits associated with limiting insulin dose and regimen complexity, the specific advantages the DPP-4 inhibitor drug class on hypoglycemia and weight gain could justify combining DPP-4 inhibitors with insulin; additionally, a DPP-4 inhibitor may be of special value to decrease glycemic excursions that are not properly addressed by basal insulin therapy and metformin use, even after optimizing titration of the basal insulin. |
| 1914 | 23680741 | However, given the common original perception that treatment with DPP-4 inhibitors may be less beneficial with increasing disease progression because of the loss of β-cell function, the potential relevance of these agents in the setting of advanced T2DM treated with insulin was not necessarily anticipated. |
| 1915 | 23680741 | Combination therapy with DPP-4 inhibitors and insulin in patients with type 2 diabetes mellitus: what is the evidence? |
| 1916 | 23680741 | In addition to the expected benefits associated with limiting insulin dose and regimen complexity, the specific advantages the DPP-4 inhibitor drug class on hypoglycemia and weight gain could justify combining DPP-4 inhibitors with insulin; additionally, a DPP-4 inhibitor may be of special value to decrease glycemic excursions that are not properly addressed by basal insulin therapy and metformin use, even after optimizing titration of the basal insulin. |
| 1917 | 23680741 | However, given the common original perception that treatment with DPP-4 inhibitors may be less beneficial with increasing disease progression because of the loss of β-cell function, the potential relevance of these agents in the setting of advanced T2DM treated with insulin was not necessarily anticipated. |
| 1918 | 23697612 | Type 2 diabetes patients have dysfunction in incretin hormones (as glucagon-like peptide-1 or GLP-1, and glucose-dependent insulinotropic polypeptide or GIP). |
| 1919 | 23697612 | By inhibiting the dipeptidyl peptidase-4 (DPP-4) enzyme, it is possible to slow the inactivation of GLP-1 and GIP, promoting blood glucose level reduction in a glucose-dependent manner. |
| 1920 | 23700522 | Adipokine release by adipocytes differentiated at lower oxygen levels was altered, with a marked upregulation of adiponectin, IL-6 and DPP4 secretion, and reduced leptin levels compared with adipocytes differentiated at 21% O2. |
| 1921 | 23707531 | The incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the small intestine into the vasculature during a meal, and these incretins have a potential to release insulin from pancreatic beta cells of islets of Langerhans, affording a glucose-lowering action. |
| 1922 | 23707531 | Inhibitors of DPP-4, therefore, enhance the bioavailability of GLP-1 and GIP, and thus have been approved for better glycemic management in patients afflicted with type 2 diabetes mellitus (T2DM). |
| 1923 | 23711188 | Sitagliptin, a dipeptidyl-peptidase 4 (DPP-4) inhibitor, improves blood glucose control in patients with type 2 diabetes by blocking cleavage of glucagon-like peptide 1 (GLP-1). |
| 1924 | 23736544 | The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin is an attractive therapy for diabetes, as it increases insulin release and may preserve β-cell mass. |
| 1925 | 23736544 | However, sitagliptin also increases β-cell release of human islet amyloid polypeptide (hIAPP), the peptide component of islet amyloid, which is cosecreted with insulin. |
| 1926 | 23736544 | Islet amyloid deposition, β-cell mass, insulin release, and measures of exocrine pancreas pathology were determined. |
| 1927 | 23752097 | In addition to metformin, the British National Formulary (Joint Formulary Committee, 2013) lists five sulfonylureas, two meglitinides, four dipeptidyl peptidase-4 inhibitors, two glucagon-like peptide-1 agonists, an inhibitor of intestinal alpha glucosidases, a sodium-glucose co-transporter 2 inhibitor, and a thiazolidinedione. |
| 1928 | 23754616 | Type 2 diabetes is quite diverse, including the improvement of insulin sensitivity by dipeptidylpeptidase-4 (DPP-4) inhibitor, α-glucosidase inhibitors, and the protection of β-cells islet. |
| 1929 | 23754616 | Trig also normalized key enzyme related to hypertension as ACE and improved the hemoglobin A1c and lipid profiles (plasma triglyceride, HDL-cholesterol, LDL-cholesterol, and total cholesterol), and liver indices toxicity. |
| 1930 | 23790528 | Dipeptidyl peptidase-4 inhibitor anagliptin ameliorates diabetes in mice with haploinsufficiency of glucokinase on a high-fat diet. |
| 1931 | 23790888 | Dipeptidyl peptidase-IV (DPP-IV) is a serine protease involved in the degradation and inactivation of incretin hormones that act by stimulating glucose-dependent insulin secretion after meal ingestion. |
| 1932 | 23807645 | The use of incretin-based therapies, such as the dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) analogs, is growing in patients with T2DM, due to their efficacy and tolerability profiles. |
| 1933 | 23810103 | Safety, effectiveness, and cost of dipeptidyl peptidase-4 inhibitors versus intermediate acting insulin for type 2 diabetes: protocol for a systematic review and network meta-analysis. |
| 1934 | 23812835 | They exert their actions through degradation inhibition of endogenous glucagon-like peptides (GLP-1) and glucose-dependent insulinotropic peptides (GIP), with a resulting increase in glucose mediated insulin secretion and a suppression of glucagon secretion. |
| 1935 | 23812835 | Since GLP-1 is known to have an impact not only on plasma glucose levels but also to have cardiovascular protective effects there is increased speculation of whether DPP-4 inhibitors will have similar effects. |
| 1936 | 23818788 | Vildagliptin is a selective and potent dipeptidyl peptidase-4 inhibitor that improves glycemic control by inhibiting the degradation of both endogenous glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. |
| 1937 | 23824323 | The present treatment options for management of diabetes have expanded since the development of glucagon-like peptide-1 agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. |
| 1938 | 23837435 | In the present study, whey protein isolate (WPI), α-lactalbumin, β-lactoglobulin, serum albumin, and lactoferrin hydrolysates obtained by peptic digestion were investigated for their potential to serve as natural sources of DPP-IV and α-glucosidase inhibitors. |
| 1939 | 23838634 | These new agents fall under the categories of incretin-related therapies, such as glucagon-like peptide-1 mimetics, glucagon-like peptide-1 analogs, dipeptidyl peptidase-4 inhibitors, and amylin analogs. |
| 1940 | 23855508 | Data from human and experimental studies implicate that GLP-1 analogues and to a less extend DPP-4 inhibitors enhance insulin sensitivity. |
| 1941 | 23855508 | This review summarizes the current knowledge regarding the impact of GLP-1 analogues and DPP-4 inhibitors on insulin resistance. |
| 1942 | 23855508 | Data from human and experimental studies implicate that GLP-1 analogues and to a less extend DPP-4 inhibitors enhance insulin sensitivity. |
| 1943 | 23855508 | This review summarizes the current knowledge regarding the impact of GLP-1 analogues and DPP-4 inhibitors on insulin resistance. |
| 1944 | 23861159 | Efficacy of alogliptin, a dipeptidyl peptidase-4 inhibitor, on glucose parameters, the activity of the advanced glycation end product (AGE) - receptor for AGE (RAGE) axis and albuminuria in Japanese type 2 diabetes. |
| 1945 | 23872069 | Lower dipeptidyl peptidase-4 following exercise training plus weight loss is related to increased insulin sensitivity in adults with metabolic syndrome. |
| 1946 | 23872069 | Dipeptidyl peptidase-4 (DPP-4) is a circulating glycoprotein that impairs insulin-stimulated glucose uptake and is linked to obesity and metabolic syndrome. |
| 1947 | 23872069 | Therefore, we determined the effect of exercise on DPP-4 and its role in explaining exercise-induced improvements in insulin sensitivity. |
| 1948 | 23872069 | Training decreased plasma DPP-4 by 10% (421.8±30.1 vs. 378.3±32.5ng/ml; P<0.04), and the decrease in DPP-4 was associated with clamp-derived insulin sensitivity (r=-0.59; P<0.04), HOMA-IR (r=0.59; P<0.04) and fat oxidation (r=-0.54; P<0.05). |
| 1949 | 23872069 | Exercise training reduces plasma DPP-4, which may be linked to elevated insulin sensitivity and fat oxidation. |
| 1950 | 23872069 | Lower dipeptidyl peptidase-4 following exercise training plus weight loss is related to increased insulin sensitivity in adults with metabolic syndrome. |
| 1951 | 23872069 | Dipeptidyl peptidase-4 (DPP-4) is a circulating glycoprotein that impairs insulin-stimulated glucose uptake and is linked to obesity and metabolic syndrome. |
| 1952 | 23872069 | Therefore, we determined the effect of exercise on DPP-4 and its role in explaining exercise-induced improvements in insulin sensitivity. |
| 1953 | 23872069 | Training decreased plasma DPP-4 by 10% (421.8±30.1 vs. 378.3±32.5ng/ml; P<0.04), and the decrease in DPP-4 was associated with clamp-derived insulin sensitivity (r=-0.59; P<0.04), HOMA-IR (r=0.59; P<0.04) and fat oxidation (r=-0.54; P<0.05). |
| 1954 | 23872069 | Exercise training reduces plasma DPP-4, which may be linked to elevated insulin sensitivity and fat oxidation. |
| 1955 | 23872069 | Lower dipeptidyl peptidase-4 following exercise training plus weight loss is related to increased insulin sensitivity in adults with metabolic syndrome. |
| 1956 | 23872069 | Dipeptidyl peptidase-4 (DPP-4) is a circulating glycoprotein that impairs insulin-stimulated glucose uptake and is linked to obesity and metabolic syndrome. |
| 1957 | 23872069 | Therefore, we determined the effect of exercise on DPP-4 and its role in explaining exercise-induced improvements in insulin sensitivity. |
| 1958 | 23872069 | Training decreased plasma DPP-4 by 10% (421.8±30.1 vs. 378.3±32.5ng/ml; P<0.04), and the decrease in DPP-4 was associated with clamp-derived insulin sensitivity (r=-0.59; P<0.04), HOMA-IR (r=0.59; P<0.04) and fat oxidation (r=-0.54; P<0.05). |
| 1959 | 23872069 | Exercise training reduces plasma DPP-4, which may be linked to elevated insulin sensitivity and fat oxidation. |
| 1960 | 23872069 | Lower dipeptidyl peptidase-4 following exercise training plus weight loss is related to increased insulin sensitivity in adults with metabolic syndrome. |
| 1961 | 23872069 | Dipeptidyl peptidase-4 (DPP-4) is a circulating glycoprotein that impairs insulin-stimulated glucose uptake and is linked to obesity and metabolic syndrome. |
| 1962 | 23872069 | Therefore, we determined the effect of exercise on DPP-4 and its role in explaining exercise-induced improvements in insulin sensitivity. |
| 1963 | 23872069 | Training decreased plasma DPP-4 by 10% (421.8±30.1 vs. 378.3±32.5ng/ml; P<0.04), and the decrease in DPP-4 was associated with clamp-derived insulin sensitivity (r=-0.59; P<0.04), HOMA-IR (r=0.59; P<0.04) and fat oxidation (r=-0.54; P<0.05). |
| 1964 | 23872069 | Exercise training reduces plasma DPP-4, which may be linked to elevated insulin sensitivity and fat oxidation. |
| 1965 | 23872069 | Lower dipeptidyl peptidase-4 following exercise training plus weight loss is related to increased insulin sensitivity in adults with metabolic syndrome. |
| 1966 | 23872069 | Dipeptidyl peptidase-4 (DPP-4) is a circulating glycoprotein that impairs insulin-stimulated glucose uptake and is linked to obesity and metabolic syndrome. |
| 1967 | 23872069 | Therefore, we determined the effect of exercise on DPP-4 and its role in explaining exercise-induced improvements in insulin sensitivity. |
| 1968 | 23872069 | Training decreased plasma DPP-4 by 10% (421.8±30.1 vs. 378.3±32.5ng/ml; P<0.04), and the decrease in DPP-4 was associated with clamp-derived insulin sensitivity (r=-0.59; P<0.04), HOMA-IR (r=0.59; P<0.04) and fat oxidation (r=-0.54; P<0.05). |
| 1969 | 23872069 | Exercise training reduces plasma DPP-4, which may be linked to elevated insulin sensitivity and fat oxidation. |
| 1970 | 23879890 | Effects of dipeptidyl peptidase-4 inhibitors in a type 2 diabetes patient with failure of glucagon-like peptide-1 receptor agonists. |
| 1971 | 23880984 | This represents a unique distinctive feature compared to the conserved expression of dipeptidyl peptidases 8 and 9 and potential relevant DPP4 substrates such as neuropeptide Y (NPY) and receptors (NPY-receptor 1 and Neurokinin receptor). |
| 1972 | 23882374 | This article is a brief review of the current non-insulin agents for diabetes mellitus in the United States, namely, sulfonylureas, biguanides, thiazolidinediones, meglitinides, α-glucosidase inhibitors, glucacon-like peptide-1 receptor agonists, dipeptidyl-peptidase-4 inhibitors, amylin agonists, bromocriptine, and colesevelam. |
| 1973 | 23890479 | Sitagliptin is a dipeptidyl peptidase IV (DPP-IV) inhibitor that exerts an anti-hyperglycaemic effect by preventing degradation of glucagon-like peptide 1 with subsequent β-cell stimulation and potential regeneration. |
| 1974 | 23890479 | While compared to diabetic controls sitagliptin prevented increase of the CD8+/CD4+ ratio in pancreatic nodes after four weeks (0.443 ± 0.067 vs. 0.544 ± 0.131; P < 0.05), the population of Tregs in lymph nodes increased from day 0 to 28 in both treated and non-treated diabetic groups (8 ± 1.76 vs. 13.45 ± 5.07 % and 8 ± 1.76 vs. 13.19 ± 5.58 %, respectively). |
| 1975 | 23912974 | To assess the efficacy and safety of adding sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, in subjects with type 2 diabetes inadequately controlled with multiple daily insulin injections therapy (MDI). |
| 1976 | 23937815 | New hypoglycemic drugs with incretin effect (glucagon-like peptide-1 agonists and dipeptidyl peptidase 4 inhibitors), achieve, in a glucose dependent manner, an glycosylated hemoglobin reduction without hypoglycemia or increase in body weight. |
| 1977 | 23938053 | Furthermore, the 4-fluorobenzyl substituted phenylalanine derivative 6g not only displayed the potent DPP-4 inhibition with an IC50 value of 3.79 nM, but also showed better selectivity against DPP-4 over other related enzymes including DPP-7, DPP-8, and DPP-9. |
| 1978 | 23946675 | Two modes of incretin-based therapy, incretin mimetics (ie, glucagon-like peptide-1 (GLP-1) agonists) and incretin enhancers (ie, inhibitors of dipeptidyl peptidase IV (DPP-IV)), have recently been introduced into the clinical use. |
| 1979 | 23946679 | In the present report, we investigated the effect of addition of sitagliptin, the first-in-class DPP-4 inhibitor, to ongoing metformin and sulfonylurea therapy in three female Japanese patients with T2DM who refused insulin therapy. |
| 1980 | 23946724 | DPP-4 Inhibitors as Therapeutic Modulators of Immune Cell Function and Associated Cardiovascular and Renal Insulin Resistance in Obesity and Diabetes. |
| 1981 | 23946724 | In this context, multiple factors including oxidative stress, increased inflammation, and inappropriate activation of the renin-angiotensin-aldosterone and the sympathetic nervous system contribute to overweight- and obesity-induced systemic and tissue insulin resistance. |
| 1982 | 23946724 | Accordingly, this review addresses new insights into the role of DPP-4 in immune modulation and the potential beneficial effects of DPP-4 inhibitors in insulin resistance and associated CVD and CKD prevention. |
| 1983 | 23946724 | DPP-4 Inhibitors as Therapeutic Modulators of Immune Cell Function and Associated Cardiovascular and Renal Insulin Resistance in Obesity and Diabetes. |
| 1984 | 23946724 | In this context, multiple factors including oxidative stress, increased inflammation, and inappropriate activation of the renin-angiotensin-aldosterone and the sympathetic nervous system contribute to overweight- and obesity-induced systemic and tissue insulin resistance. |
| 1985 | 23946724 | Accordingly, this review addresses new insights into the role of DPP-4 in immune modulation and the potential beneficial effects of DPP-4 inhibitors in insulin resistance and associated CVD and CKD prevention. |
| 1986 | 23952467 | Data from prospective studies and clinical trials suggest that lifestyle modifications and certain antihyperglycaemic medications, including thiazolidinediones (TZDs), glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors and insulin, may preserve or enhance β-cell function. |
| 1987 | 23967137 | Preventive effect of dipeptidyl peptidase-4 inhibitor on atherosclerosis is mainly attributable to incretin's actions in nondiabetic and diabetic apolipoprotein E-null mice. |
| 1988 | 23972441 | Optimization of the series provided inhibitors with good DPP-4 potency and selectivity over other peptidases (QPP, DPP8, and FAP). |
| 1989 | 23984879 | Advanced glycation end products evoke endothelial cell damage by stimulating soluble dipeptidyl peptidase-4 production and its interaction with mannose 6-phosphate/insulin-like growth factor II receptor. |
| 1990 | 23986202 | Secretion of GLP-1 has been suggested to be impaired in T2D and in conditions associated with hyperlipidemia and insulin resistance. |
| 1991 | 23986202 | However, little is known about the regulation of L-cell viability/function, the effects of insulin signaling, or the potential effects of stable GLP-1 analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors. |
| 1992 | 23986202 | We determined effects of insulin as well as possible autocrine action of GLP-1 on viability/apoptosis of GLP-1-secreting cells in the presence/absence of palmitate, while also assessing direct effects on function. |
| 1993 | 23986202 | Our results show that palmitate induced production of reactive oxygen species and caspase-3 activity and reduced cell viability are significantly attenuated by preincubation with insulin/exendin-4. |
| 1994 | 23986202 | The indicated lipoprotective effect of insulin/exendin-4 was not detectable in the presence of the GLP-1 receptor (GLP-1R) antagonist exendin (9-39) and attenuated in response to pharmacological inhibition of exchange protein activated by cAMP (Epac) signaling, while protein kinase A inhibition had no significant effect. |
| 1995 | 23986202 | Insulin/exendin-4 also significantly stimulate acute and long-term GLP-1 secretion in the presence of glucose, suggesting novel beneficial effects of insulin signaling and GLP-1R activation on glycemia through enhanced mass of GLP-1-producing cells and enhanced GLP-1 secretion. |
| 1996 | 23986202 | In addition, the effects of insulin indicate that not only is GLP-1 important for insulin secretion but altered insulin signaling may contribute to an altered GLP-1 secretion. |
| 1997 | 23990203 | Association between urinary albumin excretion and low-density lipoprotein heterogeneity following treatment of type 2 diabetes patients with the dipeptidyl peptidase-4 inhibitor, vildagliptin: a pilot study. |
| 1998 | 23992745 | As GLP-1 is rapidly degraded by protease dipeptidyl peptidase-4, a number of degradation-resistant GLP-1 receptor agonists (GLP-1RAs) have been developed for the treatment of Type 2 diabetes mellitus. |
| 1999 | 20709939 | Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. |
| 2000 | 20709939 | In addition, [(3)H]liraglutide and [(3)H]GLP-1(7-37) were incubated in vitro with dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) to compare the metabolite profiles and characterize the degradation products of liraglutide. |
| 2001 | 20709939 | Similarly to GLP-1, liraglutide was cleaved in vitro by DPP-IV in the Ala8-Glu9 position of the N terminus and degraded by NEP into several metabolites. |
| 2002 | 20709939 | The chromatographic retention time of DPP-IV-truncated liraglutide correlated well with the primary human plasma metabolite [GLP-1(9-37)], and some of the NEP degradation products eluted very close to both plasma metabolites. |
| 2003 | 20709939 | In conclusion, liraglutide is metabolized in vitro by DPP-IV and NEP in a manner similar to that of native GLP-1, although at a much slower rate. |
| 2004 | 20709939 | The metabolite profiles suggest that both DPP-IV and NEP are also involved in the in vivo degradation of liraglutide. |
| 2005 | 20709939 | Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. |
| 2006 | 20709939 | In addition, [(3)H]liraglutide and [(3)H]GLP-1(7-37) were incubated in vitro with dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) to compare the metabolite profiles and characterize the degradation products of liraglutide. |
| 2007 | 20709939 | Similarly to GLP-1, liraglutide was cleaved in vitro by DPP-IV in the Ala8-Glu9 position of the N terminus and degraded by NEP into several metabolites. |
| 2008 | 20709939 | The chromatographic retention time of DPP-IV-truncated liraglutide correlated well with the primary human plasma metabolite [GLP-1(9-37)], and some of the NEP degradation products eluted very close to both plasma metabolites. |
| 2009 | 20709939 | In conclusion, liraglutide is metabolized in vitro by DPP-IV and NEP in a manner similar to that of native GLP-1, although at a much slower rate. |
| 2010 | 20709939 | The metabolite profiles suggest that both DPP-IV and NEP are also involved in the in vivo degradation of liraglutide. |
| 2011 | 20709939 | Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. |
| 2012 | 20709939 | In addition, [(3)H]liraglutide and [(3)H]GLP-1(7-37) were incubated in vitro with dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) to compare the metabolite profiles and characterize the degradation products of liraglutide. |
| 2013 | 20709939 | Similarly to GLP-1, liraglutide was cleaved in vitro by DPP-IV in the Ala8-Glu9 position of the N terminus and degraded by NEP into several metabolites. |
| 2014 | 20709939 | The chromatographic retention time of DPP-IV-truncated liraglutide correlated well with the primary human plasma metabolite [GLP-1(9-37)], and some of the NEP degradation products eluted very close to both plasma metabolites. |
| 2015 | 20709939 | In conclusion, liraglutide is metabolized in vitro by DPP-IV and NEP in a manner similar to that of native GLP-1, although at a much slower rate. |
| 2016 | 20709939 | The metabolite profiles suggest that both DPP-IV and NEP are also involved in the in vivo degradation of liraglutide. |
| 2017 | 20709939 | Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. |
| 2018 | 20709939 | In addition, [(3)H]liraglutide and [(3)H]GLP-1(7-37) were incubated in vitro with dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) to compare the metabolite profiles and characterize the degradation products of liraglutide. |
| 2019 | 20709939 | Similarly to GLP-1, liraglutide was cleaved in vitro by DPP-IV in the Ala8-Glu9 position of the N terminus and degraded by NEP into several metabolites. |
| 2020 | 20709939 | The chromatographic retention time of DPP-IV-truncated liraglutide correlated well with the primary human plasma metabolite [GLP-1(9-37)], and some of the NEP degradation products eluted very close to both plasma metabolites. |
| 2021 | 20709939 | In conclusion, liraglutide is metabolized in vitro by DPP-IV and NEP in a manner similar to that of native GLP-1, although at a much slower rate. |
| 2022 | 20709939 | The metabolite profiles suggest that both DPP-IV and NEP are also involved in the in vivo degradation of liraglutide. |