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Gene Information
Gene symbol: GIPR
Gene name: gastric inhibitory polypeptide receptor
HGNC ID: 4271
Related Genes
| # | Gene Symbol | Number of hits |
| 1 | ACACA | 1 hits |
| 2 | ADCY5 | 1 hits |
| 3 | ADCY7 | 1 hits |
| 4 | ADIPOQ | 1 hits |
| 5 | CALCR | 1 hits |
| 6 | CARTPT | 1 hits |
| 7 | CD36 | 1 hits |
| 8 | CRHR1 | 1 hits |
| 9 | CRY2 | 1 hits |
| 10 | CYSLTR2 | 1 hits |
| 11 | DGKB | 1 hits |
| 12 | ECD | 1 hits |
| 13 | FFAR1 | 1 hits |
| 14 | FOXO1 | 1 hits |
| 15 | GCG | 1 hits |
| 16 | GCGR | 1 hits |
| 17 | GCK | 1 hits |
| 18 | GCKR | 1 hits |
| 19 | GHRH | 1 hits |
| 20 | GHRHR | 1 hits |
| 21 | GIP | 1 hits |
| 22 | GLIS3 | 1 hits |
| 23 | GLP1R | 1 hits |
| 24 | GNAI2 | 1 hits |
| 25 | GPBAR1 | 1 hits |
| 26 | GPR176 | 1 hits |
| 27 | IGF1 | 1 hits |
| 28 | INS | 1 hits |
| 29 | INSR | 1 hits |
| 30 | IRS1 | 1 hits |
| 31 | JAG2 | 1 hits |
| 32 | JUN | 1 hits |
| 33 | KCNJ11 | 1 hits |
| 34 | LEP | 1 hits |
| 35 | LPL | 1 hits |
| 36 | MADD | 1 hits |
| 37 | MC2R | 1 hits |
| 38 | NKX6-1 | 1 hits |
| 39 | NKX6-2 | 1 hits |
| 40 | NPY | 1 hits |
| 41 | PAX6 | 1 hits |
| 42 | PC | 1 hits |
| 43 | PDHX | 1 hits |
| 44 | PDX1 | 1 hits |
| 45 | POMC | 1 hits |
| 46 | PPARA | 1 hits |
| 47 | PROX1 | 1 hits |
| 48 | PTH | 1 hits |
| 49 | PTHR1 | 1 hits |
| 50 | RETN | 1 hits |
| 51 | SCTR | 1 hits |
| 52 | SERPINE1 | 1 hits |
| 53 | SLC30A8 | 1 hits |
| 54 | SP1 | 1 hits |
| 55 | SP3 | 1 hits |
| 56 | TCF7L2 | 1 hits |
| 57 | TRH | 1 hits |
| 58 | UCP2 | 1 hits |
| 59 | VIP | 1 hits |
| 60 | VPS13C | 1 hits |
Related Sentences
| # | PMID | Sentence |
| 1 | 7556958 | Glucose-dependent insulinotropic polypeptide (GIP) is a hormone secreted by the endocrine K-cells from the duodenum that stimulates glucose-induced insulin secretion. |
| 2 | 7556958 | Here, we present the molecular characterization of the human pancreatic islet GIP receptor. cDNA clones for the GIP receptor were isolated from a human pancreatic islet cDNA library. |
| 3 | 7556958 | The receptor protein sequence was 81% identical to that of the rat GIP receptor. |
| 4 | 7556958 | GIP binding was displaced by < 20% by 1 mumol/l glucagon, glucagon-like peptide (GLP-I)(7-36) amide, vasoactive intestinal peptide, and secretin. |
| 5 | 7556958 | These data will help study the physiology and pathophysiology of the human GIP receptor. |
| 6 | 7556958 | Glucose-dependent insulinotropic polypeptide (GIP) is a hormone secreted by the endocrine K-cells from the duodenum that stimulates glucose-induced insulin secretion. |
| 7 | 7556958 | Here, we present the molecular characterization of the human pancreatic islet GIP receptor. cDNA clones for the GIP receptor were isolated from a human pancreatic islet cDNA library. |
| 8 | 7556958 | The receptor protein sequence was 81% identical to that of the rat GIP receptor. |
| 9 | 7556958 | GIP binding was displaced by < 20% by 1 mumol/l glucagon, glucagon-like peptide (GLP-I)(7-36) amide, vasoactive intestinal peptide, and secretin. |
| 10 | 7556958 | These data will help study the physiology and pathophysiology of the human GIP receptor. |
| 11 | 7556958 | Glucose-dependent insulinotropic polypeptide (GIP) is a hormone secreted by the endocrine K-cells from the duodenum that stimulates glucose-induced insulin secretion. |
| 12 | 7556958 | Here, we present the molecular characterization of the human pancreatic islet GIP receptor. cDNA clones for the GIP receptor were isolated from a human pancreatic islet cDNA library. |
| 13 | 7556958 | The receptor protein sequence was 81% identical to that of the rat GIP receptor. |
| 14 | 7556958 | GIP binding was displaced by < 20% by 1 mumol/l glucagon, glucagon-like peptide (GLP-I)(7-36) amide, vasoactive intestinal peptide, and secretin. |
| 15 | 7556958 | These data will help study the physiology and pathophysiology of the human GIP receptor. |
| 16 | 7589426 | Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma. |
| 17 | 7589426 | Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the regulation of postprandial insulin secretion and proinsulin gene expression of pancreatic beta-cells. |
| 18 | 7589426 | This study demonstrates the molecular cloning of a cDNA for the GIP-receptor from a human insulinoma lambda gt11 cDNA library. |
| 19 | 7589426 | Homology to the GIP receptor from rat or hamster was 79% and 81%, respectively. |
| 20 | 7589426 | At 1 microM, exendin-4 and (9-39)amide weakly reduced GIP-binding (25%) whereas secretin, glucagon, glucagon-like peptide-1, vasoactive intestinal polypeptide, peptide histidine-isoleucine, and pituitary adenylyl cyclase activating peptide were without effect. |
| 21 | 7589426 | Northern analysis revealed one transcript of human GIP receptor mRNA with an apparent size of 5.5 kb. |
| 22 | 7589426 | The exact understanding of GIP receptor regulation and signal transduction will aid in the understanding of the incretin hormone's failure to exert its biological action at the pancreatic B-cell in type II diabetes mellitus. |
| 23 | 7589426 | Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma. |
| 24 | 7589426 | Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the regulation of postprandial insulin secretion and proinsulin gene expression of pancreatic beta-cells. |
| 25 | 7589426 | This study demonstrates the molecular cloning of a cDNA for the GIP-receptor from a human insulinoma lambda gt11 cDNA library. |
| 26 | 7589426 | Homology to the GIP receptor from rat or hamster was 79% and 81%, respectively. |
| 27 | 7589426 | At 1 microM, exendin-4 and (9-39)amide weakly reduced GIP-binding (25%) whereas secretin, glucagon, glucagon-like peptide-1, vasoactive intestinal polypeptide, peptide histidine-isoleucine, and pituitary adenylyl cyclase activating peptide were without effect. |
| 28 | 7589426 | Northern analysis revealed one transcript of human GIP receptor mRNA with an apparent size of 5.5 kb. |
| 29 | 7589426 | The exact understanding of GIP receptor regulation and signal transduction will aid in the understanding of the incretin hormone's failure to exert its biological action at the pancreatic B-cell in type II diabetes mellitus. |
| 30 | 7589426 | Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma. |
| 31 | 7589426 | Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the regulation of postprandial insulin secretion and proinsulin gene expression of pancreatic beta-cells. |
| 32 | 7589426 | This study demonstrates the molecular cloning of a cDNA for the GIP-receptor from a human insulinoma lambda gt11 cDNA library. |
| 33 | 7589426 | Homology to the GIP receptor from rat or hamster was 79% and 81%, respectively. |
| 34 | 7589426 | At 1 microM, exendin-4 and (9-39)amide weakly reduced GIP-binding (25%) whereas secretin, glucagon, glucagon-like peptide-1, vasoactive intestinal polypeptide, peptide histidine-isoleucine, and pituitary adenylyl cyclase activating peptide were without effect. |
| 35 | 7589426 | Northern analysis revealed one transcript of human GIP receptor mRNA with an apparent size of 5.5 kb. |
| 36 | 7589426 | The exact understanding of GIP receptor regulation and signal transduction will aid in the understanding of the incretin hormone's failure to exert its biological action at the pancreatic B-cell in type II diabetes mellitus. |
| 37 | 7589426 | Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma. |
| 38 | 7589426 | Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the regulation of postprandial insulin secretion and proinsulin gene expression of pancreatic beta-cells. |
| 39 | 7589426 | This study demonstrates the molecular cloning of a cDNA for the GIP-receptor from a human insulinoma lambda gt11 cDNA library. |
| 40 | 7589426 | Homology to the GIP receptor from rat or hamster was 79% and 81%, respectively. |
| 41 | 7589426 | At 1 microM, exendin-4 and (9-39)amide weakly reduced GIP-binding (25%) whereas secretin, glucagon, glucagon-like peptide-1, vasoactive intestinal polypeptide, peptide histidine-isoleucine, and pituitary adenylyl cyclase activating peptide were without effect. |
| 42 | 7589426 | Northern analysis revealed one transcript of human GIP receptor mRNA with an apparent size of 5.5 kb. |
| 43 | 7589426 | The exact understanding of GIP receptor regulation and signal transduction will aid in the understanding of the incretin hormone's failure to exert its biological action at the pancreatic B-cell in type II diabetes mellitus. |
| 44 | 7589426 | Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma. |
| 45 | 7589426 | Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the regulation of postprandial insulin secretion and proinsulin gene expression of pancreatic beta-cells. |
| 46 | 7589426 | This study demonstrates the molecular cloning of a cDNA for the GIP-receptor from a human insulinoma lambda gt11 cDNA library. |
| 47 | 7589426 | Homology to the GIP receptor from rat or hamster was 79% and 81%, respectively. |
| 48 | 7589426 | At 1 microM, exendin-4 and (9-39)amide weakly reduced GIP-binding (25%) whereas secretin, glucagon, glucagon-like peptide-1, vasoactive intestinal polypeptide, peptide histidine-isoleucine, and pituitary adenylyl cyclase activating peptide were without effect. |
| 49 | 7589426 | Northern analysis revealed one transcript of human GIP receptor mRNA with an apparent size of 5.5 kb. |
| 50 | 7589426 | The exact understanding of GIP receptor regulation and signal transduction will aid in the understanding of the incretin hormone's failure to exert its biological action at the pancreatic B-cell in type II diabetes mellitus. |
| 51 | 7664683 | In the present study we cloned a rat islet GIP receptor complementary DNA (GIP-R1) to answer several important questions regarding the ligand-binding and intracellular signaling properties of the GP receptor. |
| 52 | 7664683 | Surprisingly, exendin-(9-39) [Ex-(9-39)], a GLP-1 receptor antagonist, and Ex-4-(1-39), a GLP-1 receptor agonist, demonstrated some affinity for the GIP receptor, with 39% and 21% displacement of [125I]spGIP, respectively, at 1 microM. |
| 53 | 7664683 | In the present study we cloned a rat islet GIP receptor complementary DNA (GIP-R1) to answer several important questions regarding the ligand-binding and intracellular signaling properties of the GP receptor. |
| 54 | 7664683 | Surprisingly, exendin-(9-39) [Ex-(9-39)], a GLP-1 receptor antagonist, and Ex-4-(1-39), a GLP-1 receptor agonist, demonstrated some affinity for the GIP receptor, with 39% and 21% displacement of [125I]spGIP, respectively, at 1 microM. |
| 55 | 8549871 | The present study shows expression at the RNA level in beta-cells of receptors for glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide I(7-36) amide (GLP-I), while RNA from islet alpha-cells hybridized only with GIP receptor cDNA. |
| 56 | 8549871 | In conclusion, these data show that stimulation of glucagon, GLP-I, and GIP receptors in rat beta-cells causes cAMP production required for insulin release, while adenylate cyclase in alpha-cells is positively regulated by GIP. |
| 57 | 8920677 | [Gastric inhibitory polypeptide (GIP) and GIP receptor (GIPR)]. |
| 58 | 8920677 | Gastric inhibitory polypeptide, originally isolated from porcine intestine, is a gastrointestinal hormone belonging to the vasoactive intestinal peptide (VIP)/glucagon/secretin family. |
| 59 | 8920677 | In vivo and in vitro experiments have indicated that GIP auguments glucose-stimulated insulin secretion, suggesting that GIP plays an important role in the regulation of insulin secretion as an incretin. |
| 60 | 8920677 | It is also suggested that GIP may be involved in the pathogenesis of non insulin-dependent diabetes mellitus (NIDDM). |
| 61 | 8920677 | We have isolated a cDNA encoding a GIP receptor from a hamster insulinoma(HIT-T15) cDNA library. |
| 62 | 8920677 | The hamster GIP receptor is a 462 amino acid protein having seven transmembrane segments. |
| 63 | 8920677 | Expression of recombinant of hamster GIP receptors in Chinese hamster ovary (CHO) cells shows that it binds specifically to GIP with high affinity (IC50 = 9.6 nM) and is positively coupled to adenylate cyclase. |
| 64 | 8920677 | RNA blot analysis reveals that a 3.8-kb GIP receptor mRNA is expressed at high levels in rat pancreatic islets as well as in HIT-T15 cells. |
| 65 | 8920677 | [Gastric inhibitory polypeptide (GIP) and GIP receptor (GIPR)]. |
| 66 | 8920677 | Gastric inhibitory polypeptide, originally isolated from porcine intestine, is a gastrointestinal hormone belonging to the vasoactive intestinal peptide (VIP)/glucagon/secretin family. |
| 67 | 8920677 | In vivo and in vitro experiments have indicated that GIP auguments glucose-stimulated insulin secretion, suggesting that GIP plays an important role in the regulation of insulin secretion as an incretin. |
| 68 | 8920677 | It is also suggested that GIP may be involved in the pathogenesis of non insulin-dependent diabetes mellitus (NIDDM). |
| 69 | 8920677 | We have isolated a cDNA encoding a GIP receptor from a hamster insulinoma(HIT-T15) cDNA library. |
| 70 | 8920677 | The hamster GIP receptor is a 462 amino acid protein having seven transmembrane segments. |
| 71 | 8920677 | Expression of recombinant of hamster GIP receptors in Chinese hamster ovary (CHO) cells shows that it binds specifically to GIP with high affinity (IC50 = 9.6 nM) and is positively coupled to adenylate cyclase. |
| 72 | 8920677 | RNA blot analysis reveals that a 3.8-kb GIP receptor mRNA is expressed at high levels in rat pancreatic islets as well as in HIT-T15 cells. |
| 73 | 8920677 | [Gastric inhibitory polypeptide (GIP) and GIP receptor (GIPR)]. |
| 74 | 8920677 | Gastric inhibitory polypeptide, originally isolated from porcine intestine, is a gastrointestinal hormone belonging to the vasoactive intestinal peptide (VIP)/glucagon/secretin family. |
| 75 | 8920677 | In vivo and in vitro experiments have indicated that GIP auguments glucose-stimulated insulin secretion, suggesting that GIP plays an important role in the regulation of insulin secretion as an incretin. |
| 76 | 8920677 | It is also suggested that GIP may be involved in the pathogenesis of non insulin-dependent diabetes mellitus (NIDDM). |
| 77 | 8920677 | We have isolated a cDNA encoding a GIP receptor from a hamster insulinoma(HIT-T15) cDNA library. |
| 78 | 8920677 | The hamster GIP receptor is a 462 amino acid protein having seven transmembrane segments. |
| 79 | 8920677 | Expression of recombinant of hamster GIP receptors in Chinese hamster ovary (CHO) cells shows that it binds specifically to GIP with high affinity (IC50 = 9.6 nM) and is positively coupled to adenylate cyclase. |
| 80 | 8920677 | RNA blot analysis reveals that a 3.8-kb GIP receptor mRNA is expressed at high levels in rat pancreatic islets as well as in HIT-T15 cells. |
| 81 | 8920677 | [Gastric inhibitory polypeptide (GIP) and GIP receptor (GIPR)]. |
| 82 | 8920677 | Gastric inhibitory polypeptide, originally isolated from porcine intestine, is a gastrointestinal hormone belonging to the vasoactive intestinal peptide (VIP)/glucagon/secretin family. |
| 83 | 8920677 | In vivo and in vitro experiments have indicated that GIP auguments glucose-stimulated insulin secretion, suggesting that GIP plays an important role in the regulation of insulin secretion as an incretin. |
| 84 | 8920677 | It is also suggested that GIP may be involved in the pathogenesis of non insulin-dependent diabetes mellitus (NIDDM). |
| 85 | 8920677 | We have isolated a cDNA encoding a GIP receptor from a hamster insulinoma(HIT-T15) cDNA library. |
| 86 | 8920677 | The hamster GIP receptor is a 462 amino acid protein having seven transmembrane segments. |
| 87 | 8920677 | Expression of recombinant of hamster GIP receptors in Chinese hamster ovary (CHO) cells shows that it binds specifically to GIP with high affinity (IC50 = 9.6 nM) and is positively coupled to adenylate cyclase. |
| 88 | 8920677 | RNA blot analysis reveals that a 3.8-kb GIP receptor mRNA is expressed at high levels in rat pancreatic islets as well as in HIT-T15 cells. |
| 89 | 8922354 | Identification of two missense mutations in the GIP receptor gene: a functional study and association analysis with NIDDM: no evidence of association with Japanese NIDDM subjects. |
| 90 | 8922354 | Gastric inhibitory polypeptide (GIP) potently stimulates insulin secretion from pancreatic islets in the presence of glucose as an incretin. |
| 91 | 8922354 | Because the insulinotropic effect of GIP is reduced in NIDDM, it should be clarified whether defects in the GIP receptor gene contribute to the impaired insulin secretion in NIDDM. |
| 92 | 8922354 | Using genomic DNA samples from Japanese NIDDM and non-NIDDM subjects, we have investigated the entire coding region of the GIP receptor gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). |
| 93 | 8922354 | Investigation of the function of GIP receptor with either of these mutations reveals a half-maximal stimulation value of GIP-induced cAMP response in Chinese hamster ovary cells expressing the GIP receptor with Gly198Cys of 6.3 +/- 1.2 x 10(-10) mol/l (n = 3), which was considerably higher than that of the normal GIP receptor, 9.4 +/- 3.8 x 10(-12) mol/l GIP (n = 3), whereas that of the GIP receptor with Glu354Gln was not significantly different from that of the normal GIP receptor. |
| 94 | 8922354 | To assess the possible role of the GIP receptor gene in genetic susceptibility to NIDDM, we have examined the allelic frequencies of Gly198Cys and Glu354Gln in NIDDM and control subjects. |
| 95 | 8922354 | Identification of two missense mutations in the GIP receptor gene: a functional study and association analysis with NIDDM: no evidence of association with Japanese NIDDM subjects. |
| 96 | 8922354 | Gastric inhibitory polypeptide (GIP) potently stimulates insulin secretion from pancreatic islets in the presence of glucose as an incretin. |
| 97 | 8922354 | Because the insulinotropic effect of GIP is reduced in NIDDM, it should be clarified whether defects in the GIP receptor gene contribute to the impaired insulin secretion in NIDDM. |
| 98 | 8922354 | Using genomic DNA samples from Japanese NIDDM and non-NIDDM subjects, we have investigated the entire coding region of the GIP receptor gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). |
| 99 | 8922354 | Investigation of the function of GIP receptor with either of these mutations reveals a half-maximal stimulation value of GIP-induced cAMP response in Chinese hamster ovary cells expressing the GIP receptor with Gly198Cys of 6.3 +/- 1.2 x 10(-10) mol/l (n = 3), which was considerably higher than that of the normal GIP receptor, 9.4 +/- 3.8 x 10(-12) mol/l GIP (n = 3), whereas that of the GIP receptor with Glu354Gln was not significantly different from that of the normal GIP receptor. |
| 100 | 8922354 | To assess the possible role of the GIP receptor gene in genetic susceptibility to NIDDM, we have examined the allelic frequencies of Gly198Cys and Glu354Gln in NIDDM and control subjects. |
| 101 | 8922354 | Identification of two missense mutations in the GIP receptor gene: a functional study and association analysis with NIDDM: no evidence of association with Japanese NIDDM subjects. |
| 102 | 8922354 | Gastric inhibitory polypeptide (GIP) potently stimulates insulin secretion from pancreatic islets in the presence of glucose as an incretin. |
| 103 | 8922354 | Because the insulinotropic effect of GIP is reduced in NIDDM, it should be clarified whether defects in the GIP receptor gene contribute to the impaired insulin secretion in NIDDM. |
| 104 | 8922354 | Using genomic DNA samples from Japanese NIDDM and non-NIDDM subjects, we have investigated the entire coding region of the GIP receptor gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). |
| 105 | 8922354 | Investigation of the function of GIP receptor with either of these mutations reveals a half-maximal stimulation value of GIP-induced cAMP response in Chinese hamster ovary cells expressing the GIP receptor with Gly198Cys of 6.3 +/- 1.2 x 10(-10) mol/l (n = 3), which was considerably higher than that of the normal GIP receptor, 9.4 +/- 3.8 x 10(-12) mol/l GIP (n = 3), whereas that of the GIP receptor with Glu354Gln was not significantly different from that of the normal GIP receptor. |
| 106 | 8922354 | To assess the possible role of the GIP receptor gene in genetic susceptibility to NIDDM, we have examined the allelic frequencies of Gly198Cys and Glu354Gln in NIDDM and control subjects. |
| 107 | 8922354 | Identification of two missense mutations in the GIP receptor gene: a functional study and association analysis with NIDDM: no evidence of association with Japanese NIDDM subjects. |
| 108 | 8922354 | Gastric inhibitory polypeptide (GIP) potently stimulates insulin secretion from pancreatic islets in the presence of glucose as an incretin. |
| 109 | 8922354 | Because the insulinotropic effect of GIP is reduced in NIDDM, it should be clarified whether defects in the GIP receptor gene contribute to the impaired insulin secretion in NIDDM. |
| 110 | 8922354 | Using genomic DNA samples from Japanese NIDDM and non-NIDDM subjects, we have investigated the entire coding region of the GIP receptor gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). |
| 111 | 8922354 | Investigation of the function of GIP receptor with either of these mutations reveals a half-maximal stimulation value of GIP-induced cAMP response in Chinese hamster ovary cells expressing the GIP receptor with Gly198Cys of 6.3 +/- 1.2 x 10(-10) mol/l (n = 3), which was considerably higher than that of the normal GIP receptor, 9.4 +/- 3.8 x 10(-12) mol/l GIP (n = 3), whereas that of the GIP receptor with Glu354Gln was not significantly different from that of the normal GIP receptor. |
| 112 | 8922354 | To assess the possible role of the GIP receptor gene in genetic susceptibility to NIDDM, we have examined the allelic frequencies of Gly198Cys and Glu354Gln in NIDDM and control subjects. |
| 113 | 8922354 | Identification of two missense mutations in the GIP receptor gene: a functional study and association analysis with NIDDM: no evidence of association with Japanese NIDDM subjects. |
| 114 | 8922354 | Gastric inhibitory polypeptide (GIP) potently stimulates insulin secretion from pancreatic islets in the presence of glucose as an incretin. |
| 115 | 8922354 | Because the insulinotropic effect of GIP is reduced in NIDDM, it should be clarified whether defects in the GIP receptor gene contribute to the impaired insulin secretion in NIDDM. |
| 116 | 8922354 | Using genomic DNA samples from Japanese NIDDM and non-NIDDM subjects, we have investigated the entire coding region of the GIP receptor gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). |
| 117 | 8922354 | Investigation of the function of GIP receptor with either of these mutations reveals a half-maximal stimulation value of GIP-induced cAMP response in Chinese hamster ovary cells expressing the GIP receptor with Gly198Cys of 6.3 +/- 1.2 x 10(-10) mol/l (n = 3), which was considerably higher than that of the normal GIP receptor, 9.4 +/- 3.8 x 10(-12) mol/l GIP (n = 3), whereas that of the GIP receptor with Glu354Gln was not significantly different from that of the normal GIP receptor. |
| 118 | 8922354 | To assess the possible role of the GIP receptor gene in genetic susceptibility to NIDDM, we have examined the allelic frequencies of Gly198Cys and Glu354Gln in NIDDM and control subjects. |
| 119 | 8928774 | In response to GIP infusion, the serum insulin concentration increased at 30 min, followed by a gradual decrease, and at 4 h, no increase in insulin levels was detected despite a sustained elevated serum GIP level. |
| 120 | 8928774 | The response to glucagon-like peptide-1 (GLP-1) was preserved, a reporter cell line (LGIPR2) stably transfected with rat GIP receptor cDNA was studied. |
| 121 | 8928774 | Additional stimulation with GIP at 16 h did not affect cAMP generation, indicating desensitization of the GIP receptor by the ligand. |
| 122 | 8928774 | The results of these studies indicate that GIP gene expression is enhanced in diabetic animals and that elevated serum GIP level induces chronic desensitization of the GIP receptor in vivo and in a stably transfected cell line. |
| 123 | 8928774 | In response to GIP infusion, the serum insulin concentration increased at 30 min, followed by a gradual decrease, and at 4 h, no increase in insulin levels was detected despite a sustained elevated serum GIP level. |
| 124 | 8928774 | The response to glucagon-like peptide-1 (GLP-1) was preserved, a reporter cell line (LGIPR2) stably transfected with rat GIP receptor cDNA was studied. |
| 125 | 8928774 | Additional stimulation with GIP at 16 h did not affect cAMP generation, indicating desensitization of the GIP receptor by the ligand. |
| 126 | 8928774 | The results of these studies indicate that GIP gene expression is enhanced in diabetic animals and that elevated serum GIP level induces chronic desensitization of the GIP receptor in vivo and in a stably transfected cell line. |
| 127 | 8928774 | In response to GIP infusion, the serum insulin concentration increased at 30 min, followed by a gradual decrease, and at 4 h, no increase in insulin levels was detected despite a sustained elevated serum GIP level. |
| 128 | 8928774 | The response to glucagon-like peptide-1 (GLP-1) was preserved, a reporter cell line (LGIPR2) stably transfected with rat GIP receptor cDNA was studied. |
| 129 | 8928774 | Additional stimulation with GIP at 16 h did not affect cAMP generation, indicating desensitization of the GIP receptor by the ligand. |
| 130 | 8928774 | The results of these studies indicate that GIP gene expression is enhanced in diabetic animals and that elevated serum GIP level induces chronic desensitization of the GIP receptor in vivo and in a stably transfected cell line. |
| 131 | 9392159 | [Gastric inhibitory polypeptide (GIP) receptor]. |
| 132 | 9794107 | Discovery of amino acid variants in the human glucose-dependent insulinotropic polypeptide (GIP) receptor: the impact on the pancreatic beta cell responses and functional expression studies in Chinese hamster fibroblast cells. |
| 133 | 9794107 | The two incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are insulinotropic factors released from the small intestine to the blood stream in response to oral glucose ingestion. |
| 134 | 9794107 | The insulinotropic effect of GLP-1 is maintained in patients with Type II (non-insulin-dependent) diabetes mellitus, whereas, for unknown reasons, the effect of GIP is diminished or lacking. |
| 135 | 9794107 | We defined the exon-intron boundaries of the human GIP receptor, made a mutational analysis of the gene and identified two amino acid substitutions, A207 V and E354Q. |
| 136 | 9794107 | Investigation of the function of the two GIP receptor variants in Chinese hamster fibroblasts showed, however, that the GIP-induced cAMP formation and the binding of GIP to cells expressing the variant receptors were not different from the findings in cells expressing the wildtype GIP receptor. |
| 137 | 9794107 | In conclusion, amino acid variants in the GIP receptor are not associated with random Type II diabetes in patients of Danish Caucasian origin or with altered GIP binding and GIP-induced cAMP production when stably transfected in Chinese hamster fibroblasts. |
| 138 | 9794107 | Discovery of amino acid variants in the human glucose-dependent insulinotropic polypeptide (GIP) receptor: the impact on the pancreatic beta cell responses and functional expression studies in Chinese hamster fibroblast cells. |
| 139 | 9794107 | The two incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are insulinotropic factors released from the small intestine to the blood stream in response to oral glucose ingestion. |
| 140 | 9794107 | The insulinotropic effect of GLP-1 is maintained in patients with Type II (non-insulin-dependent) diabetes mellitus, whereas, for unknown reasons, the effect of GIP is diminished or lacking. |
| 141 | 9794107 | We defined the exon-intron boundaries of the human GIP receptor, made a mutational analysis of the gene and identified two amino acid substitutions, A207 V and E354Q. |
| 142 | 9794107 | Investigation of the function of the two GIP receptor variants in Chinese hamster fibroblasts showed, however, that the GIP-induced cAMP formation and the binding of GIP to cells expressing the variant receptors were not different from the findings in cells expressing the wildtype GIP receptor. |
| 143 | 9794107 | In conclusion, amino acid variants in the GIP receptor are not associated with random Type II diabetes in patients of Danish Caucasian origin or with altered GIP binding and GIP-induced cAMP production when stably transfected in Chinese hamster fibroblasts. |
| 144 | 9794107 | Discovery of amino acid variants in the human glucose-dependent insulinotropic polypeptide (GIP) receptor: the impact on the pancreatic beta cell responses and functional expression studies in Chinese hamster fibroblast cells. |
| 145 | 9794107 | The two incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are insulinotropic factors released from the small intestine to the blood stream in response to oral glucose ingestion. |
| 146 | 9794107 | The insulinotropic effect of GLP-1 is maintained in patients with Type II (non-insulin-dependent) diabetes mellitus, whereas, for unknown reasons, the effect of GIP is diminished or lacking. |
| 147 | 9794107 | We defined the exon-intron boundaries of the human GIP receptor, made a mutational analysis of the gene and identified two amino acid substitutions, A207 V and E354Q. |
| 148 | 9794107 | Investigation of the function of the two GIP receptor variants in Chinese hamster fibroblasts showed, however, that the GIP-induced cAMP formation and the binding of GIP to cells expressing the variant receptors were not different from the findings in cells expressing the wildtype GIP receptor. |
| 149 | 9794107 | In conclusion, amino acid variants in the GIP receptor are not associated with random Type II diabetes in patients of Danish Caucasian origin or with altered GIP binding and GIP-induced cAMP production when stably transfected in Chinese hamster fibroblasts. |
| 150 | 9794107 | Discovery of amino acid variants in the human glucose-dependent insulinotropic polypeptide (GIP) receptor: the impact on the pancreatic beta cell responses and functional expression studies in Chinese hamster fibroblast cells. |
| 151 | 9794107 | The two incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are insulinotropic factors released from the small intestine to the blood stream in response to oral glucose ingestion. |
| 152 | 9794107 | The insulinotropic effect of GLP-1 is maintained in patients with Type II (non-insulin-dependent) diabetes mellitus, whereas, for unknown reasons, the effect of GIP is diminished or lacking. |
| 153 | 9794107 | We defined the exon-intron boundaries of the human GIP receptor, made a mutational analysis of the gene and identified two amino acid substitutions, A207 V and E354Q. |
| 154 | 9794107 | Investigation of the function of the two GIP receptor variants in Chinese hamster fibroblasts showed, however, that the GIP-induced cAMP formation and the binding of GIP to cells expressing the variant receptors were not different from the findings in cells expressing the wildtype GIP receptor. |
| 155 | 9794107 | In conclusion, amino acid variants in the GIP receptor are not associated with random Type II diabetes in patients of Danish Caucasian origin or with altered GIP binding and GIP-induced cAMP production when stably transfected in Chinese hamster fibroblasts. |
| 156 | 10455124 | Characterization of the carboxyl-terminal domain of the rat glucose-dependent insulinotropic polypeptide (GIP) receptor. |
| 157 | 10455124 | Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone involved in the regulation of insulin secretion. |
| 158 | 10455124 | In non-insulin-dependent diabetes mellitus insulin responses to GIP are blunted, possibly due to altered signal transduction or reduced receptor number. |
| 159 | 10455124 | The majority of the GIP receptor CT is therefore not required for signaling, a minimum chain length of approximately 405 amino acids is needed for receptor expression, and serines 426 and 427 are important for regulating rate of receptor internalization. |
| 160 | 10455124 | Characterization of the carboxyl-terminal domain of the rat glucose-dependent insulinotropic polypeptide (GIP) receptor. |
| 161 | 10455124 | Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone involved in the regulation of insulin secretion. |
| 162 | 10455124 | In non-insulin-dependent diabetes mellitus insulin responses to GIP are blunted, possibly due to altered signal transduction or reduced receptor number. |
| 163 | 10455124 | The majority of the GIP receptor CT is therefore not required for signaling, a minimum chain length of approximately 405 amino acids is needed for receptor expression, and serines 426 and 427 are important for regulating rate of receptor internalization. |
| 164 | 10611300 | Mice with a targeted mutation of the gastric inhibitory polypeptide (GIP) receptor gene (GIPR) were generated to determine the role of GIP as a mediator of signals from the gut to pancreatic beta cells. |
| 165 | 10611300 | GIPR-/- mice have higher blood glucose levels with impaired initial insulin response after oral glucose load. |
| 166 | 10611300 | Although blood glucose levels after meal ingestion are not increased by high-fat diet in GIPR+/+ mice because of compensatory higher insulin secretion, they are significantly increased in GIPR-/- mice because of the lack of such enhancement. |
| 167 | 10611300 | Accordingly, early insulin secretion mediated by GIP determines glucose tolerance after oral glucose load in vivo, and because GIP plays an important role in the compensatory enhancement of insulin secretion produced by a high insulin demand, a defect in this entero-insular axis may contribute to the pathogenesis of diabetes. |
| 168 | 10611300 | Mice with a targeted mutation of the gastric inhibitory polypeptide (GIP) receptor gene (GIPR) were generated to determine the role of GIP as a mediator of signals from the gut to pancreatic beta cells. |
| 169 | 10611300 | GIPR-/- mice have higher blood glucose levels with impaired initial insulin response after oral glucose load. |
| 170 | 10611300 | Although blood glucose levels after meal ingestion are not increased by high-fat diet in GIPR+/+ mice because of compensatory higher insulin secretion, they are significantly increased in GIPR-/- mice because of the lack of such enhancement. |
| 171 | 10611300 | Accordingly, early insulin secretion mediated by GIP determines glucose tolerance after oral glucose load in vivo, and because GIP plays an important role in the compensatory enhancement of insulin secretion produced by a high insulin demand, a defect in this entero-insular axis may contribute to the pathogenesis of diabetes. |
| 172 | 10611300 | Mice with a targeted mutation of the gastric inhibitory polypeptide (GIP) receptor gene (GIPR) were generated to determine the role of GIP as a mediator of signals from the gut to pancreatic beta cells. |
| 173 | 10611300 | GIPR-/- mice have higher blood glucose levels with impaired initial insulin response after oral glucose load. |
| 174 | 10611300 | Although blood glucose levels after meal ingestion are not increased by high-fat diet in GIPR+/+ mice because of compensatory higher insulin secretion, they are significantly increased in GIPR-/- mice because of the lack of such enhancement. |
| 175 | 10611300 | Accordingly, early insulin secretion mediated by GIP determines glucose tolerance after oral glucose load in vivo, and because GIP plays an important role in the compensatory enhancement of insulin secretion produced by a high insulin demand, a defect in this entero-insular axis may contribute to the pathogenesis of diabetes. |
| 176 | 10666005 | Accordingly, it was later renamed glucose-dependent insulinotropic polypeptide because its action on insulin release depends upon an increase in circulating levels of glucose. |
| 177 | 10666005 | The GIP receptor is a G-protein-coupled receptor belonging to the family of secretin/VIP receptors. |
| 178 | 10666005 | GIP receptor mRNA is widely distributed in peripheral organs, including the pancreas, gut, adipose tissue, heart, adrenal cortex, and brain, suggesting it may have other functions in addition to the ones mentioned above. |
| 179 | 10666005 | In addition to stimulating insulin release, GIP has been shown to amplify the effect of insulin on target tissues. |
| 180 | 10666005 | In adipose tissue, GIP has been reported to (1) stimulate fatty acid synthesis, (2) enhance insulin-stimulated incorporation of fatty acids into triglycerides, (3) increase insulin receptor affinity, and (4) increase sensitivity of insulin-stimulated glucose transport. |
| 181 | 10666005 | Accordingly, it was later renamed glucose-dependent insulinotropic polypeptide because its action on insulin release depends upon an increase in circulating levels of glucose. |
| 182 | 10666005 | The GIP receptor is a G-protein-coupled receptor belonging to the family of secretin/VIP receptors. |
| 183 | 10666005 | GIP receptor mRNA is widely distributed in peripheral organs, including the pancreas, gut, adipose tissue, heart, adrenal cortex, and brain, suggesting it may have other functions in addition to the ones mentioned above. |
| 184 | 10666005 | In addition to stimulating insulin release, GIP has been shown to amplify the effect of insulin on target tissues. |
| 185 | 10666005 | In adipose tissue, GIP has been reported to (1) stimulate fatty acid synthesis, (2) enhance insulin-stimulated incorporation of fatty acids into triglycerides, (3) increase insulin receptor affinity, and (4) increase sensitivity of insulin-stimulated glucose transport. |
| 186 | 11158012 | Aberrant gastric inhibitory polypeptide (GIP) receptor expression in bilaterally hyperplastic adrenals or unilateral adrenal adenomas is a rare form of adrenal hyperfunction. |
| 187 | 11158012 | In the present study, we describe a novel case of a GIP receptor-expressive adrenocortical adenomatous nodule, detected incidentally by computed tomography scanning in a 41-yr-old lady with hirsutism but no clinical signs of Cushing's syndrome, on physical examination. |
| 188 | 11158012 | The expression of the GIP receptor in tumor cells, but not in the adjacent normal adrenal, was demonstrated by RT-PCR), using specific oligonucleotide probes for this receptor. |
| 189 | 11158012 | Thus, aberrant expression of the GIP receptor does not exclusively involve cells of a zona fasciculata phenotype, as previously reported, but may also occur in other types of differentiated adrenocortical cells. |
| 190 | 11158012 | Aberrant gastric inhibitory polypeptide (GIP) receptor expression in bilaterally hyperplastic adrenals or unilateral adrenal adenomas is a rare form of adrenal hyperfunction. |
| 191 | 11158012 | In the present study, we describe a novel case of a GIP receptor-expressive adrenocortical adenomatous nodule, detected incidentally by computed tomography scanning in a 41-yr-old lady with hirsutism but no clinical signs of Cushing's syndrome, on physical examination. |
| 192 | 11158012 | The expression of the GIP receptor in tumor cells, but not in the adjacent normal adrenal, was demonstrated by RT-PCR), using specific oligonucleotide probes for this receptor. |
| 193 | 11158012 | Thus, aberrant expression of the GIP receptor does not exclusively involve cells of a zona fasciculata phenotype, as previously reported, but may also occur in other types of differentiated adrenocortical cells. |
| 194 | 11158012 | Aberrant gastric inhibitory polypeptide (GIP) receptor expression in bilaterally hyperplastic adrenals or unilateral adrenal adenomas is a rare form of adrenal hyperfunction. |
| 195 | 11158012 | In the present study, we describe a novel case of a GIP receptor-expressive adrenocortical adenomatous nodule, detected incidentally by computed tomography scanning in a 41-yr-old lady with hirsutism but no clinical signs of Cushing's syndrome, on physical examination. |
| 196 | 11158012 | The expression of the GIP receptor in tumor cells, but not in the adjacent normal adrenal, was demonstrated by RT-PCR), using specific oligonucleotide probes for this receptor. |
| 197 | 11158012 | Thus, aberrant expression of the GIP receptor does not exclusively involve cells of a zona fasciculata phenotype, as previously reported, but may also occur in other types of differentiated adrenocortical cells. |
| 198 | 11158012 | Aberrant gastric inhibitory polypeptide (GIP) receptor expression in bilaterally hyperplastic adrenals or unilateral adrenal adenomas is a rare form of adrenal hyperfunction. |
| 199 | 11158012 | In the present study, we describe a novel case of a GIP receptor-expressive adrenocortical adenomatous nodule, detected incidentally by computed tomography scanning in a 41-yr-old lady with hirsutism but no clinical signs of Cushing's syndrome, on physical examination. |
| 200 | 11158012 | The expression of the GIP receptor in tumor cells, but not in the adjacent normal adrenal, was demonstrated by RT-PCR), using specific oligonucleotide probes for this receptor. |
| 201 | 11158012 | Thus, aberrant expression of the GIP receptor does not exclusively involve cells of a zona fasciculata phenotype, as previously reported, but may also occur in other types of differentiated adrenocortical cells. |
| 202 | 11334402 | Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that is released postprandially from the small intestine and acts in concert with glucagon-like peptide (GLP)-1 to potentiate glucose-induced insulin secretion from the pancreatic beta-cell. |
| 203 | 11334402 | In type 2 diabetes, there is a decreased responsiveness of the pancreas to GIP; however, the insulin response to GLP-1 remains intact. |
| 204 | 11334402 | The literature suggests that the ineffectiveness of GIP in type 2 diabetes may be a result of chronic homologous desensitization of the GIP receptor. |
| 205 | 11334402 | The hypothesis of the present study is that one cause of decreased responsiveness to GIP in type 2 diabetes is an inappropriate expression of the GIP receptor in the pancreatic islet. |
| 206 | 11334402 | GIP also potently stimulated first-phase insulin secretion from isolated perifused islets (10.3 +/- 3.0 x basal), and GIP and GLP-1 potentiated insulin secretion from the perfused pancreas (6 x control area under the curve [AUC]) from lean animals. |
| 207 | 11334402 | GIP yielded no significant effect in the Vancouver diabetic fatty Zucker (VDF) rat pancreases, whereas GLP-1 elicited an eightfold increase of insulin secretion from the perfused VDF pancreas. |
| 208 | 11334402 | Finally, the expression of both GIP receptor mRNA and protein was decreased in islets from VDF rats. |
| 209 | 11334402 | Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that is released postprandially from the small intestine and acts in concert with glucagon-like peptide (GLP)-1 to potentiate glucose-induced insulin secretion from the pancreatic beta-cell. |
| 210 | 11334402 | In type 2 diabetes, there is a decreased responsiveness of the pancreas to GIP; however, the insulin response to GLP-1 remains intact. |
| 211 | 11334402 | The literature suggests that the ineffectiveness of GIP in type 2 diabetes may be a result of chronic homologous desensitization of the GIP receptor. |
| 212 | 11334402 | The hypothesis of the present study is that one cause of decreased responsiveness to GIP in type 2 diabetes is an inappropriate expression of the GIP receptor in the pancreatic islet. |
| 213 | 11334402 | GIP also potently stimulated first-phase insulin secretion from isolated perifused islets (10.3 +/- 3.0 x basal), and GIP and GLP-1 potentiated insulin secretion from the perfused pancreas (6 x control area under the curve [AUC]) from lean animals. |
| 214 | 11334402 | GIP yielded no significant effect in the Vancouver diabetic fatty Zucker (VDF) rat pancreases, whereas GLP-1 elicited an eightfold increase of insulin secretion from the perfused VDF pancreas. |
| 215 | 11334402 | Finally, the expression of both GIP receptor mRNA and protein was decreased in islets from VDF rats. |
| 216 | 11334402 | Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that is released postprandially from the small intestine and acts in concert with glucagon-like peptide (GLP)-1 to potentiate glucose-induced insulin secretion from the pancreatic beta-cell. |
| 217 | 11334402 | In type 2 diabetes, there is a decreased responsiveness of the pancreas to GIP; however, the insulin response to GLP-1 remains intact. |
| 218 | 11334402 | The literature suggests that the ineffectiveness of GIP in type 2 diabetes may be a result of chronic homologous desensitization of the GIP receptor. |
| 219 | 11334402 | The hypothesis of the present study is that one cause of decreased responsiveness to GIP in type 2 diabetes is an inappropriate expression of the GIP receptor in the pancreatic islet. |
| 220 | 11334402 | GIP also potently stimulated first-phase insulin secretion from isolated perifused islets (10.3 +/- 3.0 x basal), and GIP and GLP-1 potentiated insulin secretion from the perfused pancreas (6 x control area under the curve [AUC]) from lean animals. |
| 221 | 11334402 | GIP yielded no significant effect in the Vancouver diabetic fatty Zucker (VDF) rat pancreases, whereas GLP-1 elicited an eightfold increase of insulin secretion from the perfused VDF pancreas. |
| 222 | 11334402 | Finally, the expression of both GIP receptor mRNA and protein was decreased in islets from VDF rats. |
| 223 | 11343800 | Due to the requirement for an elevated glucose concentration for activity, the incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1, have potential in the treatment of non-insulin-dependent diabetes mellitus. |
| 224 | 11343800 | Peptides were screened for stimulation of cyclic AMP (cAMP) accumulation in Chinese hamster ovary cells transfected with the rat islet GIP receptor. |
| 225 | 11343800 | Competitive-binding displacement studies indicated that these peptides were low-affinity ligands for the GIP receptor. |
| 226 | 11343800 | Intravenous infusion of GIP(1-42) (1 pmol/min/100 g) with a concurrent intraperitoneal glucose load (1 g/kg) significantly reduced circulating blood glucose excursions through stimulation of insulin release. |
| 227 | 11343800 | Due to the requirement for an elevated glucose concentration for activity, the incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1, have potential in the treatment of non-insulin-dependent diabetes mellitus. |
| 228 | 11343800 | Peptides were screened for stimulation of cyclic AMP (cAMP) accumulation in Chinese hamster ovary cells transfected with the rat islet GIP receptor. |
| 229 | 11343800 | Competitive-binding displacement studies indicated that these peptides were low-affinity ligands for the GIP receptor. |
| 230 | 11343800 | Intravenous infusion of GIP(1-42) (1 pmol/min/100 g) with a concurrent intraperitoneal glucose load (1 g/kg) significantly reduced circulating blood glucose excursions through stimulation of insulin release. |
| 231 | 11820780 | In CHL cells expressing the human GIP receptor, (Pro(3))GIP antagonized the cyclic adenosine monophosphate (cAMP) stimulatory ability of 10(-7) M native GIP, with an IC(50) value of 2.6 microM. |
| 232 | 11820780 | In the clonal pancreatic beta cell line BRIN-BD11, (Pro(3))GIP over the concentration range 10(-13) to 10(-8) M dose dependently inhibited GIP-stimulated (10(-7) M) insulin release (1.2- to 1.7-fold; P < 0.05 to P < 0.001). |
| 233 | 11820780 | In obese diabetic (ob/ob) mice, intraperitoneal administration of (Pro(3))GIP (25 nmol/kg body wt) countered the ability of native GIP to stimulate plasma insulin (2.4-fold decrease; P < 0.001) and lower the glycemic excursion (1.5-fold decrease; P < 0.001) induced by a glucose load (18 mmol/kg body wt). |
| 234 | 11820780 | Collectively these data demonstrate that (Pro(3))GIP is a novel and potent enzyme-resistant GIP receptor antagonist capable of blocking the ability of native GIP to increase cAMP, stimulate insulin secretion, and improve glucose homeostasis in a commonly employed animal model of type 2 diabetes. |
| 235 | 11820780 | In CHL cells expressing the human GIP receptor, (Pro(3))GIP antagonized the cyclic adenosine monophosphate (cAMP) stimulatory ability of 10(-7) M native GIP, with an IC(50) value of 2.6 microM. |
| 236 | 11820780 | In the clonal pancreatic beta cell line BRIN-BD11, (Pro(3))GIP over the concentration range 10(-13) to 10(-8) M dose dependently inhibited GIP-stimulated (10(-7) M) insulin release (1.2- to 1.7-fold; P < 0.05 to P < 0.001). |
| 237 | 11820780 | In obese diabetic (ob/ob) mice, intraperitoneal administration of (Pro(3))GIP (25 nmol/kg body wt) countered the ability of native GIP to stimulate plasma insulin (2.4-fold decrease; P < 0.001) and lower the glycemic excursion (1.5-fold decrease; P < 0.001) induced by a glucose load (18 mmol/kg body wt). |
| 238 | 11820780 | Collectively these data demonstrate that (Pro(3))GIP is a novel and potent enzyme-resistant GIP receptor antagonist capable of blocking the ability of native GIP to increase cAMP, stimulate insulin secretion, and improve glucose homeostasis in a commonly employed animal model of type 2 diabetes. |
| 239 | 11872663 | A series of synthetic GIP peptides modified at the NH(2)-terminus were screened in vitro for resistance to dipeptidyl peptidase IV (DP IV) degradation and potency to stimulate cyclic AMP and affinity for the transfected rat GIP receptor. |
| 240 | 11872663 | , or fa/fa Vancouver Diabetic Fatty (VDF) Zucker rats, both GIP and [D-Ala(2)]GIP significantly reduced glycemic excursions during a concurrent oral glucose tolerance test via stimulation of insulin release. |
| 241 | 12068290 | Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with insulin resistance. |
| 242 | 12068290 | In contrast, mice lacking the GIP receptor (Gipr(-/-)) fed a high-fat diet were clearly protected from both the obesity and the insulin resistance. |
| 243 | 12068290 | Moreover, double-homozygous mice (Gipr(-/-), Lep(ob)/Lep(ob)) generated by crossbreeding Gipr(-/-) and obese ob/ob (Lep(ob)/Lep(ob)) mice gained less weight and had lower adiposity than Lep(ob)/Lep(ob) mice. |
| 244 | 12068290 | Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with insulin resistance. |
| 245 | 12068290 | In contrast, mice lacking the GIP receptor (Gipr(-/-)) fed a high-fat diet were clearly protected from both the obesity and the insulin resistance. |
| 246 | 12068290 | Moreover, double-homozygous mice (Gipr(-/-), Lep(ob)/Lep(ob)) generated by crossbreeding Gipr(-/-) and obese ob/ob (Lep(ob)/Lep(ob)) mice gained less weight and had lower adiposity than Lep(ob)/Lep(ob) mice. |
| 247 | 12102645 | Gastric inhibitory polypeptide analogues: do they have a therapeutic role in diabetes mellitus similar to that of glucagon-like Peptide-1? |
| 248 | 12102645 | Gastric inhibitory polypeptide (GIP, also called glucose-dependent insulinotropic polypeptide) and glucagon-like peptide-1 (GLP-1) are peptide hormones from the gut that enhance nutrient-stimulated insulin secretion (the 'incretin' effect). |
| 249 | 12102645 | Judging from experiments in mice with targeted deletions of GIP and GLP-1 receptors, the incretin effect is essential for normal glucose tolerance. |
| 250 | 12102645 | The explanation seems to be that both the secretion of GLP-1 and the effect of GIP are impaired (whereas both the secretion of GIP and the effect of GLP-1 are near normal). |
| 251 | 12102645 | The known genetic variations in the GIP receptor sequence are not associated with type 2 diabetes mellitus, but a defective insulinotropic effect of GIP may be found in first degree relatives of the patients, suggesting a genetic background for the defect. |
| 252 | 12102645 | Whereas GLP-1 and its analogues are attractive as therapeutic agents for type 2 diabetes mellitus, analogues of GIP are unlikely to be effective. |
| 253 | 12102645 | On the other hand, GIP seems to play an important role in lipid metabolism, promoting the disposal of ingested lipids, and mice with a targeted deletion of the GIP receptor do not become obese when exposed to a high-fat diet. |
| 254 | 12102645 | Gastric inhibitory polypeptide analogues: do they have a therapeutic role in diabetes mellitus similar to that of glucagon-like Peptide-1? |
| 255 | 12102645 | Gastric inhibitory polypeptide (GIP, also called glucose-dependent insulinotropic polypeptide) and glucagon-like peptide-1 (GLP-1) are peptide hormones from the gut that enhance nutrient-stimulated insulin secretion (the 'incretin' effect). |
| 256 | 12102645 | Judging from experiments in mice with targeted deletions of GIP and GLP-1 receptors, the incretin effect is essential for normal glucose tolerance. |
| 257 | 12102645 | The explanation seems to be that both the secretion of GLP-1 and the effect of GIP are impaired (whereas both the secretion of GIP and the effect of GLP-1 are near normal). |
| 258 | 12102645 | The known genetic variations in the GIP receptor sequence are not associated with type 2 diabetes mellitus, but a defective insulinotropic effect of GIP may be found in first degree relatives of the patients, suggesting a genetic background for the defect. |
| 259 | 12102645 | Whereas GLP-1 and its analogues are attractive as therapeutic agents for type 2 diabetes mellitus, analogues of GIP are unlikely to be effective. |
| 260 | 12102645 | On the other hand, GIP seems to play an important role in lipid metabolism, promoting the disposal of ingested lipids, and mice with a targeted deletion of the GIP receptor do not become obese when exposed to a high-fat diet. |
| 261 | 12150711 | Enhanced cAMP generation and insulin-releasing potency of two novel Tyr1-modified enzyme-resistant forms of glucose-dependent insulinotropic polypeptide is associated with significant antihyperglycaemic activity in spontaneous obesity-diabetes. |
| 262 | 12150711 | Glucose-dependent insulinotropic polypeptide (GIP) is an important incretin hormone, which potentiates glucose-induced insulin secretion. |
| 263 | 12150711 | In Chinese hamster lung (CHL) cells expressing the cloned human GIP receptor, both analogues exhibited a 2-fold increase in cAMP-generating potency compared with native GIP (EC(50) values of 9.4, 10.0 and 18.2 nM respectively). |
| 264 | 12150711 | This was associated with a significantly greater AUC for insulin (2.1-fold; P <0.001) for both analogues compared with native GIP. |
| 265 | 12475913 | A novel pathway for regulation of glucose-dependent insulinotropic polypeptide (GIP) receptor expression in beta cells. |
| 266 | 12475913 | Glucose-dependent insulinotropic polypeptide (GIP) is secreted postprandially and acts in concert with glucose to stimulate insulin secretion from the pancreas. |
| 267 | 12475913 | Here, we describe a novel pathway for the regulation of GIP receptor (GIPR) expression within clonal beta-cell lines, pancreatic islets, and in vivo. |
| 268 | 12475913 | High (25 mM) glucose was able to significantly reduce GIPR mRNA levels in INS(832/13) cells after only 6 h. |
| 269 | 12475913 | In contrast, palmitic acid (2 mM) and WY 14643 (100 microM) stimulated approximate doublings of GIPR expression in INS(832/13) cells under low (5.5 mM), but not high (25 mM), glucose conditions, suggesting that fat can regulate GIPR expression via PPARalpha in a glucose-dependent manner. |
| 270 | 12475913 | Both MK-886, an antagonist of PPARalpha, and a dominant negative form of PPARalpha transfected into INS(832/13) cells caused a significant reduction in GIPR expression in low, but not high, glucose conditions. |
| 271 | 12475913 | Finally, in hyperglycemic clamped rats, there was a 70% reduction in GIPR expression in the islets and a 71% reduction in GIP-stimulated insulin secretion from the perfused pancreas. |
| 272 | 12475913 | Thus, evidence is presented that the GIPR is controlled at normoglycemia by the fatty acid load on the islet; however, when exposed to hyperglycemic conditions, the GIPR is down-regulated, which may contribute to the decreased responsiveness to GIP that is observed in type 2 diabetes. |
| 273 | 12475913 | A novel pathway for regulation of glucose-dependent insulinotropic polypeptide (GIP) receptor expression in beta cells. |
| 274 | 12475913 | Glucose-dependent insulinotropic polypeptide (GIP) is secreted postprandially and acts in concert with glucose to stimulate insulin secretion from the pancreas. |
| 275 | 12475913 | Here, we describe a novel pathway for the regulation of GIP receptor (GIPR) expression within clonal beta-cell lines, pancreatic islets, and in vivo. |
| 276 | 12475913 | High (25 mM) glucose was able to significantly reduce GIPR mRNA levels in INS(832/13) cells after only 6 h. |
| 277 | 12475913 | In contrast, palmitic acid (2 mM) and WY 14643 (100 microM) stimulated approximate doublings of GIPR expression in INS(832/13) cells under low (5.5 mM), but not high (25 mM), glucose conditions, suggesting that fat can regulate GIPR expression via PPARalpha in a glucose-dependent manner. |
| 278 | 12475913 | Both MK-886, an antagonist of PPARalpha, and a dominant negative form of PPARalpha transfected into INS(832/13) cells caused a significant reduction in GIPR expression in low, but not high, glucose conditions. |
| 279 | 12475913 | Finally, in hyperglycemic clamped rats, there was a 70% reduction in GIPR expression in the islets and a 71% reduction in GIP-stimulated insulin secretion from the perfused pancreas. |
| 280 | 12475913 | Thus, evidence is presented that the GIPR is controlled at normoglycemia by the fatty acid load on the islet; however, when exposed to hyperglycemic conditions, the GIPR is down-regulated, which may contribute to the decreased responsiveness to GIP that is observed in type 2 diabetes. |
| 281 | 12475913 | A novel pathway for regulation of glucose-dependent insulinotropic polypeptide (GIP) receptor expression in beta cells. |
| 282 | 12475913 | Glucose-dependent insulinotropic polypeptide (GIP) is secreted postprandially and acts in concert with glucose to stimulate insulin secretion from the pancreas. |
| 283 | 12475913 | Here, we describe a novel pathway for the regulation of GIP receptor (GIPR) expression within clonal beta-cell lines, pancreatic islets, and in vivo. |
| 284 | 12475913 | High (25 mM) glucose was able to significantly reduce GIPR mRNA levels in INS(832/13) cells after only 6 h. |
| 285 | 12475913 | In contrast, palmitic acid (2 mM) and WY 14643 (100 microM) stimulated approximate doublings of GIPR expression in INS(832/13) cells under low (5.5 mM), but not high (25 mM), glucose conditions, suggesting that fat can regulate GIPR expression via PPARalpha in a glucose-dependent manner. |
| 286 | 12475913 | Both MK-886, an antagonist of PPARalpha, and a dominant negative form of PPARalpha transfected into INS(832/13) cells caused a significant reduction in GIPR expression in low, but not high, glucose conditions. |
| 287 | 12475913 | Finally, in hyperglycemic clamped rats, there was a 70% reduction in GIPR expression in the islets and a 71% reduction in GIP-stimulated insulin secretion from the perfused pancreas. |
| 288 | 12475913 | Thus, evidence is presented that the GIPR is controlled at normoglycemia by the fatty acid load on the islet; however, when exposed to hyperglycemic conditions, the GIPR is down-regulated, which may contribute to the decreased responsiveness to GIP that is observed in type 2 diabetes. |
| 289 | 12475913 | A novel pathway for regulation of glucose-dependent insulinotropic polypeptide (GIP) receptor expression in beta cells. |
| 290 | 12475913 | Glucose-dependent insulinotropic polypeptide (GIP) is secreted postprandially and acts in concert with glucose to stimulate insulin secretion from the pancreas. |
| 291 | 12475913 | Here, we describe a novel pathway for the regulation of GIP receptor (GIPR) expression within clonal beta-cell lines, pancreatic islets, and in vivo. |
| 292 | 12475913 | High (25 mM) glucose was able to significantly reduce GIPR mRNA levels in INS(832/13) cells after only 6 h. |
| 293 | 12475913 | In contrast, palmitic acid (2 mM) and WY 14643 (100 microM) stimulated approximate doublings of GIPR expression in INS(832/13) cells under low (5.5 mM), but not high (25 mM), glucose conditions, suggesting that fat can regulate GIPR expression via PPARalpha in a glucose-dependent manner. |
| 294 | 12475913 | Both MK-886, an antagonist of PPARalpha, and a dominant negative form of PPARalpha transfected into INS(832/13) cells caused a significant reduction in GIPR expression in low, but not high, glucose conditions. |
| 295 | 12475913 | Finally, in hyperglycemic clamped rats, there was a 70% reduction in GIPR expression in the islets and a 71% reduction in GIP-stimulated insulin secretion from the perfused pancreas. |
| 296 | 12475913 | Thus, evidence is presented that the GIPR is controlled at normoglycemia by the fatty acid load on the islet; however, when exposed to hyperglycemic conditions, the GIPR is down-regulated, which may contribute to the decreased responsiveness to GIP that is observed in type 2 diabetes. |
| 297 | 12475913 | A novel pathway for regulation of glucose-dependent insulinotropic polypeptide (GIP) receptor expression in beta cells. |
| 298 | 12475913 | Glucose-dependent insulinotropic polypeptide (GIP) is secreted postprandially and acts in concert with glucose to stimulate insulin secretion from the pancreas. |
| 299 | 12475913 | Here, we describe a novel pathway for the regulation of GIP receptor (GIPR) expression within clonal beta-cell lines, pancreatic islets, and in vivo. |
| 300 | 12475913 | High (25 mM) glucose was able to significantly reduce GIPR mRNA levels in INS(832/13) cells after only 6 h. |
| 301 | 12475913 | In contrast, palmitic acid (2 mM) and WY 14643 (100 microM) stimulated approximate doublings of GIPR expression in INS(832/13) cells under low (5.5 mM), but not high (25 mM), glucose conditions, suggesting that fat can regulate GIPR expression via PPARalpha in a glucose-dependent manner. |
| 302 | 12475913 | Both MK-886, an antagonist of PPARalpha, and a dominant negative form of PPARalpha transfected into INS(832/13) cells caused a significant reduction in GIPR expression in low, but not high, glucose conditions. |
| 303 | 12475913 | Finally, in hyperglycemic clamped rats, there was a 70% reduction in GIPR expression in the islets and a 71% reduction in GIP-stimulated insulin secretion from the perfused pancreas. |
| 304 | 12475913 | Thus, evidence is presented that the GIPR is controlled at normoglycemia by the fatty acid load on the islet; however, when exposed to hyperglycemic conditions, the GIPR is down-regulated, which may contribute to the decreased responsiveness to GIP that is observed in type 2 diabetes. |
| 305 | 12475913 | A novel pathway for regulation of glucose-dependent insulinotropic polypeptide (GIP) receptor expression in beta cells. |
| 306 | 12475913 | Glucose-dependent insulinotropic polypeptide (GIP) is secreted postprandially and acts in concert with glucose to stimulate insulin secretion from the pancreas. |
| 307 | 12475913 | Here, we describe a novel pathway for the regulation of GIP receptor (GIPR) expression within clonal beta-cell lines, pancreatic islets, and in vivo. |
| 308 | 12475913 | High (25 mM) glucose was able to significantly reduce GIPR mRNA levels in INS(832/13) cells after only 6 h. |
| 309 | 12475913 | In contrast, palmitic acid (2 mM) and WY 14643 (100 microM) stimulated approximate doublings of GIPR expression in INS(832/13) cells under low (5.5 mM), but not high (25 mM), glucose conditions, suggesting that fat can regulate GIPR expression via PPARalpha in a glucose-dependent manner. |
| 310 | 12475913 | Both MK-886, an antagonist of PPARalpha, and a dominant negative form of PPARalpha transfected into INS(832/13) cells caused a significant reduction in GIPR expression in low, but not high, glucose conditions. |
| 311 | 12475913 | Finally, in hyperglycemic clamped rats, there was a 70% reduction in GIPR expression in the islets and a 71% reduction in GIP-stimulated insulin secretion from the perfused pancreas. |
| 312 | 12475913 | Thus, evidence is presented that the GIPR is controlled at normoglycemia by the fatty acid load on the islet; however, when exposed to hyperglycemic conditions, the GIPR is down-regulated, which may contribute to the decreased responsiveness to GIP that is observed in type 2 diabetes. |
| 313 | 12475913 | A novel pathway for regulation of glucose-dependent insulinotropic polypeptide (GIP) receptor expression in beta cells. |
| 314 | 12475913 | Glucose-dependent insulinotropic polypeptide (GIP) is secreted postprandially and acts in concert with glucose to stimulate insulin secretion from the pancreas. |
| 315 | 12475913 | Here, we describe a novel pathway for the regulation of GIP receptor (GIPR) expression within clonal beta-cell lines, pancreatic islets, and in vivo. |
| 316 | 12475913 | High (25 mM) glucose was able to significantly reduce GIPR mRNA levels in INS(832/13) cells after only 6 h. |
| 317 | 12475913 | In contrast, palmitic acid (2 mM) and WY 14643 (100 microM) stimulated approximate doublings of GIPR expression in INS(832/13) cells under low (5.5 mM), but not high (25 mM), glucose conditions, suggesting that fat can regulate GIPR expression via PPARalpha in a glucose-dependent manner. |
| 318 | 12475913 | Both MK-886, an antagonist of PPARalpha, and a dominant negative form of PPARalpha transfected into INS(832/13) cells caused a significant reduction in GIPR expression in low, but not high, glucose conditions. |
| 319 | 12475913 | Finally, in hyperglycemic clamped rats, there was a 70% reduction in GIPR expression in the islets and a 71% reduction in GIP-stimulated insulin secretion from the perfused pancreas. |
| 320 | 12475913 | Thus, evidence is presented that the GIPR is controlled at normoglycemia by the fatty acid load on the islet; however, when exposed to hyperglycemic conditions, the GIPR is down-regulated, which may contribute to the decreased responsiveness to GIP that is observed in type 2 diabetes. |
| 321 | 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. |
| 322 | 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). |
| 323 | 12525257 | Following incubation in plasma, (Ser2)GIP had a reduced hydrolysis rate compared with native GIP, while (Gly2)GIP was completely stable. |
| 324 | 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. |
| 325 | 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. |
| 326 | 12525257 | This enhanced glucose-lowering ability was coupled to a significantly raised (P<0.01) and more protracted insulin response compared with GIP. |
| 327 | 12540373 | The incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut hormones that act via the enteroinsular axis to potentiate insulin secretion from the pancreas in a glucose-dependent manner. |
| 328 | 12540373 | Both GLP-1 receptor and GIP receptor knockout mice (GLP-1R(-/-) and GIPR(-/-), respectively) have been generated to investigate the physiological importance of this axis. |
| 329 | 12540373 | Although reduced GIP action is a component of type 2 diabetes, GIPR-deficient mice exhibit only moderately impaired glucose tolerance. |
| 330 | 12540373 | Although serum total GLP-1 levels in GIPR knockout mice were unaltered, insulin responses to GLP-1 from pancreas perfusions and static islet incubations were significantly greater (40-60%) in GIPR(-/-) than in wild-type (GIPR(+/+)) mice. |
| 331 | 12540373 | Pancreatic insulin content and gene expression were reduced in GIPR(-/-) mice compared with GIPR(+/+) mice. |
| 332 | 12540373 | In conclusion, GIPR(-/-) mice exhibit altered islet structure and topography and increased islet sensitivity to GLP-1 despite a decrease in pancreatic insulin content and gene expression. |
| 333 | 12540373 | The incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut hormones that act via the enteroinsular axis to potentiate insulin secretion from the pancreas in a glucose-dependent manner. |
| 334 | 12540373 | Both GLP-1 receptor and GIP receptor knockout mice (GLP-1R(-/-) and GIPR(-/-), respectively) have been generated to investigate the physiological importance of this axis. |
| 335 | 12540373 | Although reduced GIP action is a component of type 2 diabetes, GIPR-deficient mice exhibit only moderately impaired glucose tolerance. |
| 336 | 12540373 | Although serum total GLP-1 levels in GIPR knockout mice were unaltered, insulin responses to GLP-1 from pancreas perfusions and static islet incubations were significantly greater (40-60%) in GIPR(-/-) than in wild-type (GIPR(+/+)) mice. |
| 337 | 12540373 | Pancreatic insulin content and gene expression were reduced in GIPR(-/-) mice compared with GIPR(+/+) mice. |
| 338 | 12540373 | In conclusion, GIPR(-/-) mice exhibit altered islet structure and topography and increased islet sensitivity to GLP-1 despite a decrease in pancreatic insulin content and gene expression. |
| 339 | 12540373 | The incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut hormones that act via the enteroinsular axis to potentiate insulin secretion from the pancreas in a glucose-dependent manner. |
| 340 | 12540373 | Both GLP-1 receptor and GIP receptor knockout mice (GLP-1R(-/-) and GIPR(-/-), respectively) have been generated to investigate the physiological importance of this axis. |
| 341 | 12540373 | Although reduced GIP action is a component of type 2 diabetes, GIPR-deficient mice exhibit only moderately impaired glucose tolerance. |
| 342 | 12540373 | Although serum total GLP-1 levels in GIPR knockout mice were unaltered, insulin responses to GLP-1 from pancreas perfusions and static islet incubations were significantly greater (40-60%) in GIPR(-/-) than in wild-type (GIPR(+/+)) mice. |
| 343 | 12540373 | Pancreatic insulin content and gene expression were reduced in GIPR(-/-) mice compared with GIPR(+/+) mice. |
| 344 | 12540373 | In conclusion, GIPR(-/-) mice exhibit altered islet structure and topography and increased islet sensitivity to GLP-1 despite a decrease in pancreatic insulin content and gene expression. |
| 345 | 12540373 | The incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut hormones that act via the enteroinsular axis to potentiate insulin secretion from the pancreas in a glucose-dependent manner. |
| 346 | 12540373 | Both GLP-1 receptor and GIP receptor knockout mice (GLP-1R(-/-) and GIPR(-/-), respectively) have been generated to investigate the physiological importance of this axis. |
| 347 | 12540373 | Although reduced GIP action is a component of type 2 diabetes, GIPR-deficient mice exhibit only moderately impaired glucose tolerance. |
| 348 | 12540373 | Although serum total GLP-1 levels in GIPR knockout mice were unaltered, insulin responses to GLP-1 from pancreas perfusions and static islet incubations were significantly greater (40-60%) in GIPR(-/-) than in wild-type (GIPR(+/+)) mice. |
| 349 | 12540373 | Pancreatic insulin content and gene expression were reduced in GIPR(-/-) mice compared with GIPR(+/+) mice. |
| 350 | 12540373 | In conclusion, GIPR(-/-) mice exhibit altered islet structure and topography and increased islet sensitivity to GLP-1 despite a decrease in pancreatic insulin content and gene expression. |
| 351 | 12540373 | The incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut hormones that act via the enteroinsular axis to potentiate insulin secretion from the pancreas in a glucose-dependent manner. |
| 352 | 12540373 | Both GLP-1 receptor and GIP receptor knockout mice (GLP-1R(-/-) and GIPR(-/-), respectively) have been generated to investigate the physiological importance of this axis. |
| 353 | 12540373 | Although reduced GIP action is a component of type 2 diabetes, GIPR-deficient mice exhibit only moderately impaired glucose tolerance. |
| 354 | 12540373 | Although serum total GLP-1 levels in GIPR knockout mice were unaltered, insulin responses to GLP-1 from pancreas perfusions and static islet incubations were significantly greater (40-60%) in GIPR(-/-) than in wild-type (GIPR(+/+)) mice. |
| 355 | 12540373 | Pancreatic insulin content and gene expression were reduced in GIPR(-/-) mice compared with GIPR(+/+) mice. |
| 356 | 12540373 | In conclusion, GIPR(-/-) mice exhibit altered islet structure and topography and increased islet sensitivity to GLP-1 despite a decrease in pancreatic insulin content and gene expression. |
| 357 | 12628351 | Because of the insulinotropic action of GIP, this hormone has been considered as a potential therapy of type 2 diabetes, where insulin secretion is inadequate. |
| 358 | 12628351 | However, a recent study using GIP receptor knockout mice suggests that inhibition of GIP signalling might be a new target for anti-obesity drugs. |
| 359 | 12789546 | GIP is a secreted protein, known to be released from the small intestine, which potentiates glucose-induced insulin secretion from the pancreas. |
| 360 | 12789546 | However, the expression of GIP and its receptor (GIPR) has not been previously noted in the rat retina. |
| 361 | 12789546 | We here demonstrate for the first time the expression of GIP and GIPR in the rat retina. |
| 362 | 12789546 | And we also revealed some genetic events in the early stage of diabetic retinopathy including the de novo increment of GIP and GIPR expression in the retina. |
| 363 | 12789546 | GIP is a secreted protein, known to be released from the small intestine, which potentiates glucose-induced insulin secretion from the pancreas. |
| 364 | 12789546 | However, the expression of GIP and its receptor (GIPR) has not been previously noted in the rat retina. |
| 365 | 12789546 | We here demonstrate for the first time the expression of GIP and GIPR in the rat retina. |
| 366 | 12789546 | And we also revealed some genetic events in the early stage of diabetic retinopathy including the de novo increment of GIP and GIPR expression in the retina. |
| 367 | 12789546 | GIP is a secreted protein, known to be released from the small intestine, which potentiates glucose-induced insulin secretion from the pancreas. |
| 368 | 12789546 | However, the expression of GIP and its receptor (GIPR) has not been previously noted in the rat retina. |
| 369 | 12789546 | We here demonstrate for the first time the expression of GIP and GIPR in the rat retina. |
| 370 | 12789546 | And we also revealed some genetic events in the early stage of diabetic retinopathy including the de novo increment of GIP and GIPR expression in the retina. |
| 371 | 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. |
| 372 | 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. |
| 373 | 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. |
| 374 | 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. |
| 375 | 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. |
| 376 | 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. |
| 377 | 14607102 | Glucose-dependent insulinotropic polypeptide (GIP or gastric inhibitory polypeptide) is a gastrointestinal hormone, which modulates physiological insulin secretion. |
| 378 | 14607102 | In addition, observations in transgenic GIP receptor deficient mice indicate that GIP directly links overnutrition to obesity, therein playing a crucial role in the development of obesity and related metabolic disorders. |
| 379 | 15111503 | Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are gut-derived incretins that potentiate glucose clearance following nutrient ingestion. |
| 380 | 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. |
| 381 | 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. |
| 382 | 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. |
| 383 | 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. |
| 384 | 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. |
| 385 | 15111503 | Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are gut-derived incretins that potentiate glucose clearance following nutrient ingestion. |
| 386 | 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. |
| 387 | 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. |
| 388 | 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. |
| 389 | 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. |
| 390 | 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. |
| 391 | 15206144 | [GIP receptor knockout mice]. |
| 392 | 15206144 | Gastric inhibitory polypeptide(GIP) is a gastrointestinal peptide hormone, which is secreted from duodenal endocrine K cells after absorption of glucose or fat. |
| 393 | 15206144 | To determine the further role of GIP in vivo, we generated GIP receptor-knockout mice. |
| 394 | 15206144 | [GIP receptor knockout mice]. |
| 395 | 15206144 | Gastric inhibitory polypeptide(GIP) is a gastrointestinal peptide hormone, which is secreted from duodenal endocrine K cells after absorption of glucose or fat. |
| 396 | 15206144 | To determine the further role of GIP in vivo, we generated GIP receptor-knockout mice. |
| 397 | 15493880 | Effects of short-term chemical ablation of the GIP receptor on insulin secretion, islet morphology and glucose homeostasis in mice. |
| 398 | 15493880 | In this study we have utilized a specific and enzymatically stable GIP receptor antagonist, (Pro3)GIP, to evaluate the contribution of endogenous GIP to insulin secretion and glucose homeostasis in mice. |
| 399 | 15493880 | Insulin sensitivity of 11-day (Pro3)GIP treated mice was slightly impaired 60 min post injection compared with controls. |
| 400 | 15493880 | Postprandial insulin secretion was not significantly different and no changes in pancreatic insulin content or islet morphology were observed in (Pro3)GIP treated mice. |
| 401 | 15493880 | These data indicate that ablation of GIP signaling causes a readily reversible glucose intolerance without appreciable change of insulin secretion. |
| 402 | 15493880 | Effects of short-term chemical ablation of the GIP receptor on insulin secretion, islet morphology and glucose homeostasis in mice. |
| 403 | 15493880 | In this study we have utilized a specific and enzymatically stable GIP receptor antagonist, (Pro3)GIP, to evaluate the contribution of endogenous GIP to insulin secretion and glucose homeostasis in mice. |
| 404 | 15493880 | Insulin sensitivity of 11-day (Pro3)GIP treated mice was slightly impaired 60 min post injection compared with controls. |
| 405 | 15493880 | Postprandial insulin secretion was not significantly different and no changes in pancreatic insulin content or islet morphology were observed in (Pro3)GIP treated mice. |
| 406 | 15493880 | These data indicate that ablation of GIP signaling causes a readily reversible glucose intolerance without appreciable change of insulin secretion. |
| 407 | 15522230 | Glucose-dependent insulinotropic polypeptide is an incretin hormone that stimulates insulin secretion and reduces postprandial glycaemic excursions. |
| 408 | 15522230 | This structural information could play an important role in the design of therapeutic agents based upon GIP receptor agonists. |
| 409 | 15561915 | Stimulation of insulin secretion by intravenous bolus injection and continuous infusion of gastric inhibitory polypeptide in patients with type 2 diabetes and healthy control subjects. |
| 410 | 15561915 | It was the aim of this study to determine the response of insulin secretion to different GIP doses administered by intravenous bolus injection and via continuous infusion in both healthy subjects and patients with type 2 diabetes. |
| 411 | 15561915 | Capillary and venous blood was drawn for glucose, insulin, C-peptide, and GIP. |
| 412 | 15561915 | GIP bolus administration evoked a significant increase in plasma insulin levels in both patients with type 2 diabetes and healthy subjects. |
| 413 | 15561915 | In contrast, the continuous GIP infusion led to a weak increase in insulin secretion in both healthy subjects and type 2 diabetic patients. |
| 414 | 15561915 | The dose-response relationship for the increase in insulin secretion after GIP bolus administration was similar in both groups, although at different degrees of beta-cell function. |
| 415 | 15561915 | The stimulation of insulin secretion by GIP is stronger after its bolus administration than during continuous infusion. |
| 416 | 15561915 | Even though the insulin secretory capacity is generally impaired in patients with type 2 diabetes, the relative sensitivity of insulin secretion to a bolus administration of GIP is almost preserved. |
| 417 | 15561915 | Therefore, the existence of a specific GIP receptor defect in type 2 diabetes appears unlikely. |
| 418 | 15582721 | Overexpression of a dominant negative GIP receptor in transgenic mice results in disturbed postnatal pancreatic islet and beta-cell development. |
| 419 | 15582721 | The expression of a dominant negative glucose-dependent insulinotropic polypeptide receptor (GIPRdn) under the control of the rat pro-insulin gene promoter induces severe diabetes mellitus in transgenic mice. |
| 420 | 15655707 | Physiology of GIP--a lesson from GIP receptor knockout mice. |
| 421 | 15655707 | GIP exerts its effects by binding to its specific receptor, the GIP receptor, which is expressed in various tissues including pancreatic islets, adipose tissue, and brain. |
| 422 | 15655707 | However, the physiological role of GIP has been generally thought to stimulate insulin secretion from pancreatic beta-cells, and the other actions of GIP have received little attention. |
| 423 | 15655707 | We have bred and characterized mice with a targeted mutation of the GIP receptor gene. |
| 424 | 15655707 | From these studies, we now know that GIP not only mediates early insulin secretion by acting on pancreatic beta-cells, but also links overnutrition to obesity by acting on adipocytes. |
| 425 | 15655707 | Physiology of GIP--a lesson from GIP receptor knockout mice. |
| 426 | 15655707 | GIP exerts its effects by binding to its specific receptor, the GIP receptor, which is expressed in various tissues including pancreatic islets, adipose tissue, and brain. |
| 427 | 15655707 | However, the physiological role of GIP has been generally thought to stimulate insulin secretion from pancreatic beta-cells, and the other actions of GIP have received little attention. |
| 428 | 15655707 | We have bred and characterized mice with a targeted mutation of the GIP receptor gene. |
| 429 | 15655707 | From these studies, we now know that GIP not only mediates early insulin secretion by acting on pancreatic beta-cells, but also links overnutrition to obesity by acting on adipocytes. |
| 430 | 15655707 | Physiology of GIP--a lesson from GIP receptor knockout mice. |
| 431 | 15655707 | GIP exerts its effects by binding to its specific receptor, the GIP receptor, which is expressed in various tissues including pancreatic islets, adipose tissue, and brain. |
| 432 | 15655707 | However, the physiological role of GIP has been generally thought to stimulate insulin secretion from pancreatic beta-cells, and the other actions of GIP have received little attention. |
| 433 | 15655707 | We have bred and characterized mice with a targeted mutation of the GIP receptor gene. |
| 434 | 15655707 | From these studies, we now know that GIP not only mediates early insulin secretion by acting on pancreatic beta-cells, but also links overnutrition to obesity by acting on adipocytes. |
| 435 | 15655720 | Glucose-dependent insulinotropic polypeptide (GIP) is released from K-cells in the gut after meal ingestion, and acts in concert with glucagon-like peptide 1 (GLP-1) to augment glucose-stimulated insulin secretion. |
| 436 | 15655720 | While derivatives of GLP-1 are under active investigation for the treatment of type 2 diabetes, the case is different for GIP. |
| 437 | 15655720 | However, glucose-normalisation, as is typically observed during the intravenous administration of GLP-1 in patients with type 2 diabetes, has not yet been achieved with GIP or its derivatives. |
| 438 | 15655720 | This concept has recently been reinforced by the observation that GIP receptor knock-out mice are protected from high-fat diet-induced obesity. |
| 439 | 15655720 | However, eliminating the effect of endogenous GIP may at the same time impair postprandial insulin secretion, thereby severely disturbing glucose homeostasis. |
| 440 | 15715491 | Degradation, insulin secretion, and antihyperglycemic actions of two palmitate-derivitized N-terminal pyroglutamyl analogues of glucose-dependent insulinotropic polypeptide. |
| 441 | 15715491 | In GIP-receptor transfected fibroblasts, N-pGluGIP(LysPAL(16)) and N-pGluGIP(LysPAL(37)) exhibited enhanced stimulation of cAMP production. |
| 442 | 15715491 | When administered together with glucose to ob/ob mice, the glycemic excursions were significantly less for both analogues and insulin responses were greater than native GIP. |
| 443 | 15923344 | Once-daily injections of N-AcGIP(LysPAL(37)) over a 14-day period significantly decreased plasma glucose, glycated hemoglobin, and improved glucose tolerance compared with ob/ob mice treated with saline or native GIP. |
| 444 | 15923344 | No evidence was found for GIP receptor desensitization and the metabolic effects of N-AcGIP(LysPAL(37)) were independent of any change in feeding or body weight. |
| 445 | 16046312 | Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3)GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure in obesity-related diabetes. |
| 446 | 16046312 | In this study, we investigated the effects of chemical ablation of GIP receptor (GIP-R) action on aspects of obesity-related diabetes using a stable and specific GIP-R antagonist, (Pro3)GIP. |
| 447 | 16046312 | GIP-R ablation also significantly lowered overall plasma glucose (1.4-fold; P < 0.05) and insulin (1.5-fold; P < 0.05) responses to feeding. |
| 448 | 16046312 | These changes were associated with significantly enhanced (1.6-fold; P < 0.05) insulin sensitivity in the (Pro3)GIP-treated group. |
| 449 | 16046312 | Daily injection of (Pro3)GIP reduced pancreatic insulin content (1.3-fold; P < 0.05) and partially corrected the obesity-related islet hypertrophy and beta-cell hyperplasia of ob/ob mice. |
| 450 | 16046312 | These studies highlight a role for GIP in obesity-related glucose intolerance and emphasize the potential of specific GIP-R antagonists as a new class of drugs for the alleviation of insulin resistance and treatment of type 2 diabetes. |
| 451 | 16046312 | Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3)GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure in obesity-related diabetes. |
| 452 | 16046312 | In this study, we investigated the effects of chemical ablation of GIP receptor (GIP-R) action on aspects of obesity-related diabetes using a stable and specific GIP-R antagonist, (Pro3)GIP. |
| 453 | 16046312 | GIP-R ablation also significantly lowered overall plasma glucose (1.4-fold; P < 0.05) and insulin (1.5-fold; P < 0.05) responses to feeding. |
| 454 | 16046312 | These changes were associated with significantly enhanced (1.6-fold; P < 0.05) insulin sensitivity in the (Pro3)GIP-treated group. |
| 455 | 16046312 | Daily injection of (Pro3)GIP reduced pancreatic insulin content (1.3-fold; P < 0.05) and partially corrected the obesity-related islet hypertrophy and beta-cell hyperplasia of ob/ob mice. |
| 456 | 16046312 | These studies highlight a role for GIP in obesity-related glucose intolerance and emphasize the potential of specific GIP-R antagonists as a new class of drugs for the alleviation of insulin resistance and treatment of type 2 diabetes. |
| 457 | 16046312 | Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3)GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure in obesity-related diabetes. |
| 458 | 16046312 | In this study, we investigated the effects of chemical ablation of GIP receptor (GIP-R) action on aspects of obesity-related diabetes using a stable and specific GIP-R antagonist, (Pro3)GIP. |
| 459 | 16046312 | GIP-R ablation also significantly lowered overall plasma glucose (1.4-fold; P < 0.05) and insulin (1.5-fold; P < 0.05) responses to feeding. |
| 460 | 16046312 | These changes were associated with significantly enhanced (1.6-fold; P < 0.05) insulin sensitivity in the (Pro3)GIP-treated group. |
| 461 | 16046312 | Daily injection of (Pro3)GIP reduced pancreatic insulin content (1.3-fold; P < 0.05) and partially corrected the obesity-related islet hypertrophy and beta-cell hyperplasia of ob/ob mice. |
| 462 | 16046312 | These studies highlight a role for GIP in obesity-related glucose intolerance and emphasize the potential of specific GIP-R antagonists as a new class of drugs for the alleviation of insulin resistance and treatment of type 2 diabetes. |
| 463 | 16046312 | Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3)GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure in obesity-related diabetes. |
| 464 | 16046312 | In this study, we investigated the effects of chemical ablation of GIP receptor (GIP-R) action on aspects of obesity-related diabetes using a stable and specific GIP-R antagonist, (Pro3)GIP. |
| 465 | 16046312 | GIP-R ablation also significantly lowered overall plasma glucose (1.4-fold; P < 0.05) and insulin (1.5-fold; P < 0.05) responses to feeding. |
| 466 | 16046312 | These changes were associated with significantly enhanced (1.6-fold; P < 0.05) insulin sensitivity in the (Pro3)GIP-treated group. |
| 467 | 16046312 | Daily injection of (Pro3)GIP reduced pancreatic insulin content (1.3-fold; P < 0.05) and partially corrected the obesity-related islet hypertrophy and beta-cell hyperplasia of ob/ob mice. |
| 468 | 16046312 | These studies highlight a role for GIP in obesity-related glucose intolerance and emphasize the potential of specific GIP-R antagonists as a new class of drugs for the alleviation of insulin resistance and treatment of type 2 diabetes. |
| 469 | 16105663 | Gastric inhibitory polypeptide modulates adiposity and fat oxidation under diminished insulin action. |
| 470 | 16105663 | Gut hormone gastric inhibitory polypeptide (GIP) stimulates insulin secretion from pancreatic beta-cells upon ingestion of nutrients. |
| 471 | 16105663 | Inhibition of GIP signaling prevents the onset of obesity and consequent insulin resistance induced by high-fat diet. |
| 472 | 16105663 | In this study, we investigated the role of GIP in accumulation of triglycerides into adipocytes and in fat oxidation peripherally using insulin receptor substrate (IRS)-1-deficient mice and revealed that IRS-1(-/-)GIPR(-/-) mice exhibited both reduced adiposity and ameliorated insulin resistance. |
| 473 | 16105663 | Furthermore, increased gene expression of CD36 and UCP2 in liver, and increased expression and enzyme activity of 3-hydroxyacyl-CoA dehydrogenase in skeletal muscle of IRS-1(-/-)GIPR(-/-) mice might contribute to the lower respiratory quotient and the higher fat oxidation in light phase. |
| 474 | 16105663 | These results suggest that GIP plays a crucial role in switching from fat oxidation to fat accumulation under the diminished insulin action as a potential target for secondary prevention of insulin resistance. |
| 475 | 16105663 | Gastric inhibitory polypeptide modulates adiposity and fat oxidation under diminished insulin action. |
| 476 | 16105663 | Gut hormone gastric inhibitory polypeptide (GIP) stimulates insulin secretion from pancreatic beta-cells upon ingestion of nutrients. |
| 477 | 16105663 | Inhibition of GIP signaling prevents the onset of obesity and consequent insulin resistance induced by high-fat diet. |
| 478 | 16105663 | In this study, we investigated the role of GIP in accumulation of triglycerides into adipocytes and in fat oxidation peripherally using insulin receptor substrate (IRS)-1-deficient mice and revealed that IRS-1(-/-)GIPR(-/-) mice exhibited both reduced adiposity and ameliorated insulin resistance. |
| 479 | 16105663 | Furthermore, increased gene expression of CD36 and UCP2 in liver, and increased expression and enzyme activity of 3-hydroxyacyl-CoA dehydrogenase in skeletal muscle of IRS-1(-/-)GIPR(-/-) mice might contribute to the lower respiratory quotient and the higher fat oxidation in light phase. |
| 480 | 16105663 | These results suggest that GIP plays a crucial role in switching from fat oxidation to fat accumulation under the diminished insulin action as a potential target for secondary prevention of insulin resistance. |
| 481 | 16181707 | Effects on glucose homeostasis and insulin secretion of long term activation of the glucose-dependent insulinotropic polypeptide (GIP) receptor by N-AcGIP(LysPAL37) in normal mice. |
| 482 | 16181707 | The present study was designed to assess the metabolic effects in healthy mice of long term activation of the GIP receptor by N-AcGIP(LysPAL37), a potent long-acting GIP receptor agonist. |
| 483 | 16181707 | Daily injection of N-AcGIP(LysPAL37) (25 nmol/kg body weight) for 14 days had no significant effect on food intake, body weight, glycated hemoglobin levels, non-fasting plasma glucose and insulin concentrations compared to saline treated controls. |
| 484 | 16181707 | These data indicate that long term activation of the GIP receptor by daily treatment with N-AcGIP(LysPAL37) improved glucose tolerance due to enhancement of pancreatic beta cell glucose responsiveness and insulin secretion. |
| 485 | 16181707 | Effects on glucose homeostasis and insulin secretion of long term activation of the glucose-dependent insulinotropic polypeptide (GIP) receptor by N-AcGIP(LysPAL37) in normal mice. |
| 486 | 16181707 | The present study was designed to assess the metabolic effects in healthy mice of long term activation of the GIP receptor by N-AcGIP(LysPAL37), a potent long-acting GIP receptor agonist. |
| 487 | 16181707 | Daily injection of N-AcGIP(LysPAL37) (25 nmol/kg body weight) for 14 days had no significant effect on food intake, body weight, glycated hemoglobin levels, non-fasting plasma glucose and insulin concentrations compared to saline treated controls. |
| 488 | 16181707 | These data indicate that long term activation of the GIP receptor by daily treatment with N-AcGIP(LysPAL37) improved glucose tolerance due to enhancement of pancreatic beta cell glucose responsiveness and insulin secretion. |
| 489 | 16181707 | Effects on glucose homeostasis and insulin secretion of long term activation of the glucose-dependent insulinotropic polypeptide (GIP) receptor by N-AcGIP(LysPAL37) in normal mice. |
| 490 | 16181707 | The present study was designed to assess the metabolic effects in healthy mice of long term activation of the GIP receptor by N-AcGIP(LysPAL37), a potent long-acting GIP receptor agonist. |
| 491 | 16181707 | Daily injection of N-AcGIP(LysPAL37) (25 nmol/kg body weight) for 14 days had no significant effect on food intake, body weight, glycated hemoglobin levels, non-fasting plasma glucose and insulin concentrations compared to saline treated controls. |
| 492 | 16181707 | These data indicate that long term activation of the GIP receptor by daily treatment with N-AcGIP(LysPAL37) improved glucose tolerance due to enhancement of pancreatic beta cell glucose responsiveness and insulin secretion. |
| 493 | 16378704 | Glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-induced insulin secretion. |
| 494 | 16378704 | The present study was designed to assess the insulinotropic effects of a potent long-acting GIP receptor agonist, N-AcGIP(LysPAL37), in aging mice. |
| 495 | 16403775 | Sp1/Sp3 binding is associated with cell-specific expression of the glucose-dependent insulinotropic polypeptide receptor gene. |
| 496 | 16403775 | Because aberrant GIP receptor (GIPR) expression has been implicated in abnormal GIP responses associated with type 2 diabetes mellitus and food-induced Cushing's syndrome, we sought to identify factors that regulate the GIPR. |
| 497 | 16403775 | Within this region, we identified three putative Sp1 binding motifs, located at positions -77, -60, and -50, that can specifically bind both Sp1 and Sp3. |
| 498 | 16403775 | Cotransfection of S2 Schneider cells with GIPR-luciferase chimeric constructs and either Sp1 or Sp3 expression vectors indicated that both Sp1 and the long form of Sp3 activate transcription through binding to the Sp1 sites located between -100 and -40. |
| 499 | 16403775 | Lastly, chromatin immunoprecipitation analyses revealed that both Sp1 and Sp3 bind to the GIPR promoter region in RIN38 cells. |
| 500 | 16403775 | These results indicate that cell-specific expression of GIPR is associated with the binding of the transcription factors Sp1 and Sp3 to the GIPR promoter. |
| 501 | 16403775 | Sp1/Sp3 binding is associated with cell-specific expression of the glucose-dependent insulinotropic polypeptide receptor gene. |
| 502 | 16403775 | Because aberrant GIP receptor (GIPR) expression has been implicated in abnormal GIP responses associated with type 2 diabetes mellitus and food-induced Cushing's syndrome, we sought to identify factors that regulate the GIPR. |
| 503 | 16403775 | Within this region, we identified three putative Sp1 binding motifs, located at positions -77, -60, and -50, that can specifically bind both Sp1 and Sp3. |
| 504 | 16403775 | Cotransfection of S2 Schneider cells with GIPR-luciferase chimeric constructs and either Sp1 or Sp3 expression vectors indicated that both Sp1 and the long form of Sp3 activate transcription through binding to the Sp1 sites located between -100 and -40. |
| 505 | 16403775 | Lastly, chromatin immunoprecipitation analyses revealed that both Sp1 and Sp3 bind to the GIPR promoter region in RIN38 cells. |
| 506 | 16403775 | These results indicate that cell-specific expression of GIPR is associated with the binding of the transcription factors Sp1 and Sp3 to the GIPR promoter. |
| 507 | 16403775 | Sp1/Sp3 binding is associated with cell-specific expression of the glucose-dependent insulinotropic polypeptide receptor gene. |
| 508 | 16403775 | Because aberrant GIP receptor (GIPR) expression has been implicated in abnormal GIP responses associated with type 2 diabetes mellitus and food-induced Cushing's syndrome, we sought to identify factors that regulate the GIPR. |
| 509 | 16403775 | Within this region, we identified three putative Sp1 binding motifs, located at positions -77, -60, and -50, that can specifically bind both Sp1 and Sp3. |
| 510 | 16403775 | Cotransfection of S2 Schneider cells with GIPR-luciferase chimeric constructs and either Sp1 or Sp3 expression vectors indicated that both Sp1 and the long form of Sp3 activate transcription through binding to the Sp1 sites located between -100 and -40. |
| 511 | 16403775 | Lastly, chromatin immunoprecipitation analyses revealed that both Sp1 and Sp3 bind to the GIPR promoter region in RIN38 cells. |
| 512 | 16403775 | These results indicate that cell-specific expression of GIPR is associated with the binding of the transcription factors Sp1 and Sp3 to the GIPR promoter. |
| 513 | 16403775 | Sp1/Sp3 binding is associated with cell-specific expression of the glucose-dependent insulinotropic polypeptide receptor gene. |
| 514 | 16403775 | Because aberrant GIP receptor (GIPR) expression has been implicated in abnormal GIP responses associated with type 2 diabetes mellitus and food-induced Cushing's syndrome, we sought to identify factors that regulate the GIPR. |
| 515 | 16403775 | Within this region, we identified three putative Sp1 binding motifs, located at positions -77, -60, and -50, that can specifically bind both Sp1 and Sp3. |
| 516 | 16403775 | Cotransfection of S2 Schneider cells with GIPR-luciferase chimeric constructs and either Sp1 or Sp3 expression vectors indicated that both Sp1 and the long form of Sp3 activate transcription through binding to the Sp1 sites located between -100 and -40. |
| 517 | 16403775 | Lastly, chromatin immunoprecipitation analyses revealed that both Sp1 and Sp3 bind to the GIPR promoter region in RIN38 cells. |
| 518 | 16403775 | These results indicate that cell-specific expression of GIPR is associated with the binding of the transcription factors Sp1 and Sp3 to the GIPR promoter. |
| 519 | 16409149 | Similarly, glucose-dependent insulinotropic polypeptide (GIP) receptor activation stimulates insulin secretion, enhances beta-cell proliferation, and reduces apoptosis. |
| 520 | 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. |
| 521 | 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. |
| 522 | 16451070 | Glucose-dependent insulinotropic polypeptide (GIP) is a physiological insulin releasing peptide. |
| 523 | 16451070 | We have developed two novel fatty acid derivatized GIP analogues, which bind to serum albumin and demonstrate enhanced duration of action in vivo. |
| 524 | 16451070 | GIP(Lys(16)PAL) and GIP(Lys(37)PAL) were resistant to dipeptidyl peptidase IV (DPP IV) degradation. |
| 525 | 16451070 | In vitro studies demonstrated that GIP analogues retained their ability to activate the GIP receptor through production of cAMP and to stimulate insulin secretion. |
| 526 | 16451070 | Intraperitoneal administration of GIP analogues to obese diabetic (ob/ob) mice significantly decreased the glycemic excursion and elicited increased and prolonged insulin responses compared to native GIP. |
| 527 | 16451070 | A protracted glucose-lowering effect was observed 24 h following GIP(Lys(37)PAL) administration. |
| 528 | 16469773 | Bone histomorphometrical analyses revealed that bone formation parameters in the mice lacking GIP receptor (GIPR(-/-)) were significantly lower than those of wild-type (GIPR(+/+)) mice, and that the number of osteoclasts, especially multinuclear osteoclasts, was significantly increased in GIPR(-/-) mice, indicating that GIPR(-/-) mice have high-turnover osteoporosis. |
| 529 | 16469773 | Because GIPR(-/-) mice exhibited an increased plasma calcium concentration after meal ingestion, GIP directly links calcium contained in meal to calcium deposition on bone. |
| 530 | 16469773 | Bone histomorphometrical analyses revealed that bone formation parameters in the mice lacking GIP receptor (GIPR(-/-)) were significantly lower than those of wild-type (GIPR(+/+)) mice, and that the number of osteoclasts, especially multinuclear osteoclasts, was significantly increased in GIPR(-/-) mice, indicating that GIPR(-/-) mice have high-turnover osteoporosis. |
| 531 | 16469773 | Because GIPR(-/-) mice exhibited an increased plasma calcium concentration after meal ingestion, GIP directly links calcium contained in meal to calcium deposition on bone. |
| 532 | 16675042 | Glucose-dependent insulinotropic polypeptide (GIP) is a key physiological insulin releasing peptide and potential antidiabetic agent. |
| 533 | 16675042 | The bioactivity of two modified C-terminally truncated fragment GIP peptides, GIP(1-16) and (Pro3)GIP(1-16), was examined in terms of insulin secretion and glucose homeostasis using BRIN-BD11 cells and type 2 diabetic mice. |
| 534 | 16675042 | In vitro insulin release studies demonstrated that GIP(1-16) and (Pro3)GIP(1-16) possessed weak GIP-receptor agonist and antagonistic properties, respectively. |
| 535 | 16675042 | Intraperitoneal administration of GIP(1-16) in combination with glucose to obese diabetic (ob/ob) mice did not effect the glycaemic excursion and had a marginal effect on insulin release. |
| 536 | 16675042 | Based on the established concept of a therapeutic benefit of GIP receptor antagonism in obesity-diabetes, ob/ob mice received once daily injection of (Pro3)GIP(1-16) for 14 days. |
| 537 | 16675042 | No significant effects were observed on food intake, body weight, HbA1c, glucose tolerance, metabolic response to feeding and either insulin secretion or insulin sensitivity following prolonged (Pro3)GIP(1-16) treatment. |
| 538 | 16675042 | Glucose-dependent insulinotropic polypeptide (GIP) is a key physiological insulin releasing peptide and potential antidiabetic agent. |
| 539 | 16675042 | The bioactivity of two modified C-terminally truncated fragment GIP peptides, GIP(1-16) and (Pro3)GIP(1-16), was examined in terms of insulin secretion and glucose homeostasis using BRIN-BD11 cells and type 2 diabetic mice. |
| 540 | 16675042 | In vitro insulin release studies demonstrated that GIP(1-16) and (Pro3)GIP(1-16) possessed weak GIP-receptor agonist and antagonistic properties, respectively. |
| 541 | 16675042 | Intraperitoneal administration of GIP(1-16) in combination with glucose to obese diabetic (ob/ob) mice did not effect the glycaemic excursion and had a marginal effect on insulin release. |
| 542 | 16675042 | Based on the established concept of a therapeutic benefit of GIP receptor antagonism in obesity-diabetes, ob/ob mice received once daily injection of (Pro3)GIP(1-16) for 14 days. |
| 543 | 16675042 | No significant effects were observed on food intake, body weight, HbA1c, glucose tolerance, metabolic response to feeding and either insulin secretion or insulin sensitivity following prolonged (Pro3)GIP(1-16) treatment. |
| 544 | 16859646 | Evaluation of the antidiabetic activity of DPP IV resistant N-terminally modified versus mid-chain acylated analogues of glucose-dependent insulinotropic polypeptide. |
| 545 | 16859646 | Glucose dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone with therapeutic potential for type 2 diabetes due to its insulin-releasing and antihyperglycaemic actions. |
| 546 | 16859646 | Numerous GIP analogues have now been generated exhibiting DPP IV resistance and extended bioactivity profiles. |
| 547 | 16859646 | In this study, we report a direct comparison of the long-term antidiabetic actions of three such GIP molecules, N-AcGIP, GIP(Lys(37)PAL) and N-AcGIP(Lys(37)PAL) in obese diabetic (ob/ob) mice. |
| 548 | 16859646 | Administration of either N-AcGIP, GIP(Lys(37)PAL) or N-AcGIP(Lys(37)PAL) significantly decreased non-fasting plasma glucose and improved glucose tolerance compared to saline treated controls. |
| 549 | 16859646 | The metabolic and insulin secretory responses to native GIP were also enhanced in 14-day analogue treated mice, revealing no evidence of GIP-receptor desensitization. |
| 550 | 17187081 | The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) control glucose homeostasis through well-defined actions on the islet beta cell via stimulation of insulin secretion and preservation and expansion of beta cell mass. |
| 551 | 17187081 | We examined the importance of endogenous incretin receptors for control of glucose homeostasis through analysis of Glp1r(-/-), Gipr(-/-), and double incretin receptor knockout (DIRKO) mice fed a high-fat (HF) diet. |
| 552 | 17187081 | Moreover, plasma levels of plasminogen activator inhibitor-1 and resistin failed to increase significantly in DIRKO mice after HF feeding, and the GIP receptor agonist [D-Ala(2)]GIP, but not the GLP-1 receptor agonist exendin-4, increased the levels of plasma resistin in studies of both acute and chronic administration. |
| 553 | 17187081 | The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) control glucose homeostasis through well-defined actions on the islet beta cell via stimulation of insulin secretion and preservation and expansion of beta cell mass. |
| 554 | 17187081 | We examined the importance of endogenous incretin receptors for control of glucose homeostasis through analysis of Glp1r(-/-), Gipr(-/-), and double incretin receptor knockout (DIRKO) mice fed a high-fat (HF) diet. |
| 555 | 17187081 | Moreover, plasma levels of plasminogen activator inhibitor-1 and resistin failed to increase significantly in DIRKO mice after HF feeding, and the GIP receptor agonist [D-Ala(2)]GIP, but not the GLP-1 receptor agonist exendin-4, increased the levels of plasma resistin in studies of both acute and chronic administration. |
| 556 | 17261080 | Characterisation and glucoregulatory actions of a novel acylated form of the (Pro3)GIP receptor antagonist in type 2 diabetes. |
| 557 | 17261080 | In this study, we tested the biological activity of a novel acylated form of (Pro3)glucose-dependent insulinotropic polypetide [(Pro3)GIP] prepared by conjugating palmitic acid to Lys16 to enhance its efficacy in vivo by promoting binding to albumin and extending its biological actions. |
| 558 | 17261080 | Like the parent molecule (Pro3)GIP, (Pro3)GIPLys16PAL was completely stable to the actions of DPP-IV and significantly (p<0.01 to p<0.001) inhibited GIP-stimulated cAMP production and cellular insulin secretion. |
| 559 | 17261080 | Furthermore, acute administration of (Pro3)GIPLys16PAL also significantly (p<0.05 to p<0.001) countered the glucose-lowering and insulin-releasing actions of GIP in ob/ob mice. |
| 560 | 17261080 | These data demonstrate that acylation of Lys16 with palmitic acid in (Pro3)GIP does not improve its biological effectiveness as a GIP receptor antagonist. |
| 561 | 17261080 | Characterisation and glucoregulatory actions of a novel acylated form of the (Pro3)GIP receptor antagonist in type 2 diabetes. |
| 562 | 17261080 | In this study, we tested the biological activity of a novel acylated form of (Pro3)glucose-dependent insulinotropic polypetide [(Pro3)GIP] prepared by conjugating palmitic acid to Lys16 to enhance its efficacy in vivo by promoting binding to albumin and extending its biological actions. |
| 563 | 17261080 | Like the parent molecule (Pro3)GIP, (Pro3)GIPLys16PAL was completely stable to the actions of DPP-IV and significantly (p<0.01 to p<0.001) inhibited GIP-stimulated cAMP production and cellular insulin secretion. |
| 564 | 17261080 | Furthermore, acute administration of (Pro3)GIPLys16PAL also significantly (p<0.05 to p<0.001) countered the glucose-lowering and insulin-releasing actions of GIP in ob/ob mice. |
| 565 | 17261080 | These data demonstrate that acylation of Lys16 with palmitic acid in (Pro3)GIP does not improve its biological effectiveness as a GIP receptor antagonist. |
| 566 | 17299087 | All three peptides exhibited DPP IV resistance, and significantly inhibited GIP stimulated cAMP formation and insulin secretion in GIP receptor-transfected fibroblasts and in clonal pancreatic BRIN-BD11 cells, respectively. |
| 567 | 17360984 | Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to impaired incretin effects in diabetes. |
| 568 | 17360984 | Stimulation of insulin secretion by the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) has been found to be diminished in type 2 diabetes. |
| 569 | 17360984 | Gene expression of incretin receptors, GLP-1R and GIPR, were significantly decreased in islets of 90% pancreatectomized (Px) hyperglycemic rats, with recovery when glucose levels were normalized by phlorizin. |
| 570 | 17360984 | Perifused islets isolated from hyperglycemic Px rats showed reduced insulin responses to GLP-1 and GIP. |
| 571 | 17360984 | To examine the acute effect of hyperglycemia on incretin receptor expression, a hyperglycemic clamp study was performed for 96 h with reduction of GLP-1 receptor expression but increase in GIP receptor expression. |
| 572 | 17360984 | The reduction of GLP-1 receptor expression by high glucose was prevented by dominant-negative protein kinase C (PKC)alpha overexpression, whereas GLP-1 receptor expression was reduced with wild-type PKCalpha overexpression. |
| 573 | 17360984 | Taken together, GLP-1 and GIP receptor expression is decreased with chronic hyperglycemia, and this decrease likely contributes to the impaired incretin effects found in diabetes. |
| 574 | 17360984 | Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to impaired incretin effects in diabetes. |
| 575 | 17360984 | Stimulation of insulin secretion by the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) has been found to be diminished in type 2 diabetes. |
| 576 | 17360984 | Gene expression of incretin receptors, GLP-1R and GIPR, were significantly decreased in islets of 90% pancreatectomized (Px) hyperglycemic rats, with recovery when glucose levels were normalized by phlorizin. |
| 577 | 17360984 | Perifused islets isolated from hyperglycemic Px rats showed reduced insulin responses to GLP-1 and GIP. |
| 578 | 17360984 | To examine the acute effect of hyperglycemia on incretin receptor expression, a hyperglycemic clamp study was performed for 96 h with reduction of GLP-1 receptor expression but increase in GIP receptor expression. |
| 579 | 17360984 | The reduction of GLP-1 receptor expression by high glucose was prevented by dominant-negative protein kinase C (PKC)alpha overexpression, whereas GLP-1 receptor expression was reduced with wild-type PKCalpha overexpression. |
| 580 | 17360984 | Taken together, GLP-1 and GIP receptor expression is decreased with chronic hyperglycemia, and this decrease likely contributes to the impaired incretin effects found in diabetes. |
| 581 | 17360984 | Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to impaired incretin effects in diabetes. |
| 582 | 17360984 | Stimulation of insulin secretion by the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) has been found to be diminished in type 2 diabetes. |
| 583 | 17360984 | Gene expression of incretin receptors, GLP-1R and GIPR, were significantly decreased in islets of 90% pancreatectomized (Px) hyperglycemic rats, with recovery when glucose levels were normalized by phlorizin. |
| 584 | 17360984 | Perifused islets isolated from hyperglycemic Px rats showed reduced insulin responses to GLP-1 and GIP. |
| 585 | 17360984 | To examine the acute effect of hyperglycemia on incretin receptor expression, a hyperglycemic clamp study was performed for 96 h with reduction of GLP-1 receptor expression but increase in GIP receptor expression. |
| 586 | 17360984 | The reduction of GLP-1 receptor expression by high glucose was prevented by dominant-negative protein kinase C (PKC)alpha overexpression, whereas GLP-1 receptor expression was reduced with wild-type PKCalpha overexpression. |
| 587 | 17360984 | Taken together, GLP-1 and GIP receptor expression is decreased with chronic hyperglycemia, and this decrease likely contributes to the impaired incretin effects found in diabetes. |
| 588 | 17360984 | Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to impaired incretin effects in diabetes. |
| 589 | 17360984 | Stimulation of insulin secretion by the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) has been found to be diminished in type 2 diabetes. |
| 590 | 17360984 | Gene expression of incretin receptors, GLP-1R and GIPR, were significantly decreased in islets of 90% pancreatectomized (Px) hyperglycemic rats, with recovery when glucose levels were normalized by phlorizin. |
| 591 | 17360984 | Perifused islets isolated from hyperglycemic Px rats showed reduced insulin responses to GLP-1 and GIP. |
| 592 | 17360984 | To examine the acute effect of hyperglycemia on incretin receptor expression, a hyperglycemic clamp study was performed for 96 h with reduction of GLP-1 receptor expression but increase in GIP receptor expression. |
| 593 | 17360984 | The reduction of GLP-1 receptor expression by high glucose was prevented by dominant-negative protein kinase C (PKC)alpha overexpression, whereas GLP-1 receptor expression was reduced with wild-type PKCalpha overexpression. |
| 594 | 17360984 | Taken together, GLP-1 and GIP receptor expression is decreased with chronic hyperglycemia, and this decrease likely contributes to the impaired incretin effects found in diabetes. |
| 595 | 17437246 | Gastric inhibitory polypeptide (GIP, or glucose-dependent insulinotropic polypeptide) is a 42-amino acid incretin hormone moderating glucose-induced insulin secretion. |
| 596 | 17437246 | We have studied the structure of GIP(1-30)NH2 and built a model of its G-protein coupled receptor (GPCR). |
| 597 | 17437246 | GIP(1-30)NH2 has all the structural features of peptides belonging to family B1 GPCRs, which are characterized by a coil at the N-terminal and a long C-terminal alpha-helix with or without a break. |
| 598 | 17437246 | A model of the seven transmembrane (TM) helices of the GIP receptor (GIPR) has been built on the principles of comparative protein modeling, using the crystal structure of bovine rhodopsin as a template. |
| 599 | 17437246 | The N-terminal domain of GIPR has been constructed from the NMR structure of the N-terminal of corticoptropin releasing factor receptor (CRFR), a family B1 GCPR. |
| 600 | 17437246 | On the basis of the experimental data available for some members of family B1 GPCRs, four pairs of constraints between GIP(1-30)NH2 and its receptor were used in the FTDOCK program, to build the complete model of the GIP(1-30)NH2:GIPR complex. |
| 601 | 17437246 | This work is the first complete model at the atomic level of GIP(1-30)NH2 and of the complex with its GPCR. |
| 602 | 17437246 | Gastric inhibitory polypeptide (GIP, or glucose-dependent insulinotropic polypeptide) is a 42-amino acid incretin hormone moderating glucose-induced insulin secretion. |
| 603 | 17437246 | We have studied the structure of GIP(1-30)NH2 and built a model of its G-protein coupled receptor (GPCR). |
| 604 | 17437246 | GIP(1-30)NH2 has all the structural features of peptides belonging to family B1 GPCRs, which are characterized by a coil at the N-terminal and a long C-terminal alpha-helix with or without a break. |
| 605 | 17437246 | A model of the seven transmembrane (TM) helices of the GIP receptor (GIPR) has been built on the principles of comparative protein modeling, using the crystal structure of bovine rhodopsin as a template. |
| 606 | 17437246 | The N-terminal domain of GIPR has been constructed from the NMR structure of the N-terminal of corticoptropin releasing factor receptor (CRFR), a family B1 GCPR. |
| 607 | 17437246 | On the basis of the experimental data available for some members of family B1 GPCRs, four pairs of constraints between GIP(1-30)NH2 and its receptor were used in the FTDOCK program, to build the complete model of the GIP(1-30)NH2:GIPR complex. |
| 608 | 17437246 | This work is the first complete model at the atomic level of GIP(1-30)NH2 and of the complex with its GPCR. |
| 609 | 17437246 | Gastric inhibitory polypeptide (GIP, or glucose-dependent insulinotropic polypeptide) is a 42-amino acid incretin hormone moderating glucose-induced insulin secretion. |
| 610 | 17437246 | We have studied the structure of GIP(1-30)NH2 and built a model of its G-protein coupled receptor (GPCR). |
| 611 | 17437246 | GIP(1-30)NH2 has all the structural features of peptides belonging to family B1 GPCRs, which are characterized by a coil at the N-terminal and a long C-terminal alpha-helix with or without a break. |
| 612 | 17437246 | A model of the seven transmembrane (TM) helices of the GIP receptor (GIPR) has been built on the principles of comparative protein modeling, using the crystal structure of bovine rhodopsin as a template. |
| 613 | 17437246 | The N-terminal domain of GIPR has been constructed from the NMR structure of the N-terminal of corticoptropin releasing factor receptor (CRFR), a family B1 GCPR. |
| 614 | 17437246 | On the basis of the experimental data available for some members of family B1 GPCRs, four pairs of constraints between GIP(1-30)NH2 and its receptor were used in the FTDOCK program, to build the complete model of the GIP(1-30)NH2:GIPR complex. |
| 615 | 17437246 | This work is the first complete model at the atomic level of GIP(1-30)NH2 and of the complex with its GPCR. |
| 616 | 17505054 | Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that has a potent stimulatory effect on insulin release under conditions of normal glucose tolerance. |
| 617 | 17505054 | Downregulation of GIP-R was rescued by treating isolated islets with proteasomal inhibitors lactacystin and MG-132, and the islets were once again capable of increasing intracellular cAMP levels in response to GIP. |
| 618 | 17505054 | These results suggest that the GIP-R is ubiquitated, resulting in downregulation of the actions of GIP. |
| 619 | 17505054 | Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that has a potent stimulatory effect on insulin release under conditions of normal glucose tolerance. |
| 620 | 17505054 | Downregulation of GIP-R was rescued by treating isolated islets with proteasomal inhibitors lactacystin and MG-132, and the islets were once again capable of increasing intracellular cAMP levels in response to GIP. |
| 621 | 17505054 | These results suggest that the GIP-R is ubiquitated, resulting in downregulation of the actions of GIP. |
| 622 | 17558485 | Chemical gastric inhibitory polypeptide receptor antagonism protects against obesity, insulin resistance, glucose intolerance and associated disturbances in mice fed high-fat and cafeteria diets. |
| 623 | 17624916 | Association analyses of GIP and GIPR polymorphisms with traits of the metabolic syndrome. |
| 624 | 17624916 | Glucose-dependent insulinotropic polypeptide (GIP) stimulates insulin release via interaction with its pancreatic receptor (GIP receptor (GIPR)). |
| 625 | 17624916 | To investigate whether variations in GIP and GIPR genes are associated with risk factors of the metabolic syndrome we sequenced gene regions and identified two coding SNPs (GIP Ser103Gly, GIPR Glu354Gln) and one splice site SNP (GIP rs2291726) in 47 subjects. |
| 626 | 17624916 | In conclusion, we identified a common splice site mutation (rs2291726) of the GIP gene which results in a truncated protein and provide preliminary evidence for an association of the heterozygous GIPR Glu354Gln genotype with CVD. |
| 627 | 17624916 | Association analyses of GIP and GIPR polymorphisms with traits of the metabolic syndrome. |
| 628 | 17624916 | Glucose-dependent insulinotropic polypeptide (GIP) stimulates insulin release via interaction with its pancreatic receptor (GIP receptor (GIPR)). |
| 629 | 17624916 | To investigate whether variations in GIP and GIPR genes are associated with risk factors of the metabolic syndrome we sequenced gene regions and identified two coding SNPs (GIP Ser103Gly, GIPR Glu354Gln) and one splice site SNP (GIP rs2291726) in 47 subjects. |
| 630 | 17624916 | In conclusion, we identified a common splice site mutation (rs2291726) of the GIP gene which results in a truncated protein and provide preliminary evidence for an association of the heterozygous GIPR Glu354Gln genotype with CVD. |
| 631 | 17624916 | Association analyses of GIP and GIPR polymorphisms with traits of the metabolic syndrome. |
| 632 | 17624916 | Glucose-dependent insulinotropic polypeptide (GIP) stimulates insulin release via interaction with its pancreatic receptor (GIP receptor (GIPR)). |
| 633 | 17624916 | To investigate whether variations in GIP and GIPR genes are associated with risk factors of the metabolic syndrome we sequenced gene regions and identified two coding SNPs (GIP Ser103Gly, GIPR Glu354Gln) and one splice site SNP (GIP rs2291726) in 47 subjects. |
| 634 | 17624916 | In conclusion, we identified a common splice site mutation (rs2291726) of the GIP gene which results in a truncated protein and provide preliminary evidence for an association of the heterozygous GIPR Glu354Gln genotype with CVD. |
| 635 | 17624916 | Association analyses of GIP and GIPR polymorphisms with traits of the metabolic syndrome. |
| 636 | 17624916 | Glucose-dependent insulinotropic polypeptide (GIP) stimulates insulin release via interaction with its pancreatic receptor (GIP receptor (GIPR)). |
| 637 | 17624916 | To investigate whether variations in GIP and GIPR genes are associated with risk factors of the metabolic syndrome we sequenced gene regions and identified two coding SNPs (GIP Ser103Gly, GIPR Glu354Gln) and one splice site SNP (GIP rs2291726) in 47 subjects. |
| 638 | 17624916 | In conclusion, we identified a common splice site mutation (rs2291726) of the GIP gene which results in a truncated protein and provide preliminary evidence for an association of the heterozygous GIPR Glu354Gln genotype with CVD. |
| 639 | 17654450 | These observations in animals and man suggest that GIP receptor antagonism may afford an alternative therapeutic option for treatment of obesity-diabetes. |
| 640 | 17848629 | GIP receptor antagonism reverses obesity, insulin resistance, and associated metabolic disturbances induced in mice by prolonged consumption of high-fat diet. |
| 641 | 17848629 | This study investigated the effects of administration of a stable and specific GIP receptor antagonist, (Pro(3))GIP, in mice previously fed a high-fat diet for 160 days to induce obesity and related diabetes. |
| 642 | 17848629 | Plasma glucose, glycated hemoglobin, and pancreatic insulin were restored to levels of chow-fed mice, and circulating triglyceride and cholesterol were significantly decreased. |
| 643 | 17848629 | (Pro(3))GIP treatment also significantly decreased circulating glucagon and corticosterone, but concentrations of GLP-1, GIP, resistin, and adiponectin were unchanged. |
| 644 | 17848629 | These changes were accompanied by significant improvement of insulin sensitivity, meal tolerance, and normalization of glucose tolerance in (Pro(3))GIP-treated high-fat-fed mice. |
| 645 | 17848629 | These data indicate that GIP receptor antagonism using (Pro(3))GIP provides an effective means of countering obesity and related diabetes induced by consumption of a high-fat, energy-rich diet. |
| 646 | 17848629 | GIP receptor antagonism reverses obesity, insulin resistance, and associated metabolic disturbances induced in mice by prolonged consumption of high-fat diet. |
| 647 | 17848629 | This study investigated the effects of administration of a stable and specific GIP receptor antagonist, (Pro(3))GIP, in mice previously fed a high-fat diet for 160 days to induce obesity and related diabetes. |
| 648 | 17848629 | Plasma glucose, glycated hemoglobin, and pancreatic insulin were restored to levels of chow-fed mice, and circulating triglyceride and cholesterol were significantly decreased. |
| 649 | 17848629 | (Pro(3))GIP treatment also significantly decreased circulating glucagon and corticosterone, but concentrations of GLP-1, GIP, resistin, and adiponectin were unchanged. |
| 650 | 17848629 | These changes were accompanied by significant improvement of insulin sensitivity, meal tolerance, and normalization of glucose tolerance in (Pro(3))GIP-treated high-fat-fed mice. |
| 651 | 17848629 | These data indicate that GIP receptor antagonism using (Pro(3))GIP provides an effective means of countering obesity and related diabetes induced by consumption of a high-fat, energy-rich diet. |
| 652 | 17848629 | GIP receptor antagonism reverses obesity, insulin resistance, and associated metabolic disturbances induced in mice by prolonged consumption of high-fat diet. |
| 653 | 17848629 | This study investigated the effects of administration of a stable and specific GIP receptor antagonist, (Pro(3))GIP, in mice previously fed a high-fat diet for 160 days to induce obesity and related diabetes. |
| 654 | 17848629 | Plasma glucose, glycated hemoglobin, and pancreatic insulin were restored to levels of chow-fed mice, and circulating triglyceride and cholesterol were significantly decreased. |
| 655 | 17848629 | (Pro(3))GIP treatment also significantly decreased circulating glucagon and corticosterone, but concentrations of GLP-1, GIP, resistin, and adiponectin were unchanged. |
| 656 | 17848629 | These changes were accompanied by significant improvement of insulin sensitivity, meal tolerance, and normalization of glucose tolerance in (Pro(3))GIP-treated high-fat-fed mice. |
| 657 | 17848629 | These data indicate that GIP receptor antagonism using (Pro(3))GIP provides an effective means of countering obesity and related diabetes induced by consumption of a high-fat, energy-rich diet. |
| 658 | 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. |
| 659 | 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. |
| 660 | 18054732 | This review discusses the various attributes of GLP-1 and GIP for diabetes treatment and summarises current clinical data. |
| 661 | 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. |
| 662 | 18505834 | To test this hypothesis, C57BL/6 mice and GIP-receptor knockout mice (Gipr(-/-)) were exposed to OVX or sham operation (n = 10 per group). |
| 663 | 18505834 | Cumulative food intake in OVX Gipr(-/-) animals was significantly reduced and associated with significantly lower hypothalamic mRNA expression of the orexigenic neuropeptide Y (NPY) but not of cocaine-amphetamine-related transcript (CART), melanocortin receptors (MCR-3 and MCR-4), or thyrotropin-releasing hormone (TRH). |
| 664 | 18505834 | To test this hypothesis, C57BL/6 mice and GIP-receptor knockout mice (Gipr(-/-)) were exposed to OVX or sham operation (n = 10 per group). |
| 665 | 18505834 | Cumulative food intake in OVX Gipr(-/-) animals was significantly reduced and associated with significantly lower hypothalamic mRNA expression of the orexigenic neuropeptide Y (NPY) but not of cocaine-amphetamine-related transcript (CART), melanocortin receptors (MCR-3 and MCR-4), or thyrotropin-releasing hormone (TRH). |
| 666 | 18723001 | Inhibition of GIP signaling modulates adiponectin levels under high-fat diet in mice. |
| 667 | 18723001 | In the present study, we investigated the effects of inhibition of GIP signaling on adiponectin levels after 3 weeks of HFD by comparing wild-type (WT) mice and GIP receptor-deficient (Gipr(-/-)) mice. |
| 668 | 18723001 | In HFD-fed Gipr(-/-) mice, fat oxidation was significantly increased and adiponectin mRNA levels in white adipose tissue and plasma adiponectin levels were significantly increased compared to those in HFD-fed WT mice. |
| 669 | 18723001 | In addition, the PPARalpha mRNA level was increased and the ACC mRNA level was decreased in skeletal muscle of HFD-fed Gipr(-/-) mice compared with those in HFD-fed WT mice. |
| 670 | 18723001 | These results indicate that inhibition of GIP signaling increases adiponectin levels, resulting in increased fat oxidation in peripheral tissues under HFD. |
| 671 | 18723001 | Inhibition of GIP signaling modulates adiponectin levels under high-fat diet in mice. |
| 672 | 18723001 | In the present study, we investigated the effects of inhibition of GIP signaling on adiponectin levels after 3 weeks of HFD by comparing wild-type (WT) mice and GIP receptor-deficient (Gipr(-/-)) mice. |
| 673 | 18723001 | In HFD-fed Gipr(-/-) mice, fat oxidation was significantly increased and adiponectin mRNA levels in white adipose tissue and plasma adiponectin levels were significantly increased compared to those in HFD-fed WT mice. |
| 674 | 18723001 | In addition, the PPARalpha mRNA level was increased and the ACC mRNA level was decreased in skeletal muscle of HFD-fed Gipr(-/-) mice compared with those in HFD-fed WT mice. |
| 675 | 18723001 | These results indicate that inhibition of GIP signaling increases adiponectin levels, resulting in increased fat oxidation in peripheral tissues under HFD. |
| 676 | 18723001 | Inhibition of GIP signaling modulates adiponectin levels under high-fat diet in mice. |
| 677 | 18723001 | In the present study, we investigated the effects of inhibition of GIP signaling on adiponectin levels after 3 weeks of HFD by comparing wild-type (WT) mice and GIP receptor-deficient (Gipr(-/-)) mice. |
| 678 | 18723001 | In HFD-fed Gipr(-/-) mice, fat oxidation was significantly increased and adiponectin mRNA levels in white adipose tissue and plasma adiponectin levels were significantly increased compared to those in HFD-fed WT mice. |
| 679 | 18723001 | In addition, the PPARalpha mRNA level was increased and the ACC mRNA level was decreased in skeletal muscle of HFD-fed Gipr(-/-) mice compared with those in HFD-fed WT mice. |
| 680 | 18723001 | These results indicate that inhibition of GIP signaling increases adiponectin levels, resulting in increased fat oxidation in peripheral tissues under HFD. |
| 681 | 19026698 | Prolonged GIP receptor activation using stable mini-PEGylated GIP improves glucose homeostasis and beta-cell function in age-related glucose intolerance. |
| 682 | 19026698 | GIP[mPEG] decreased glucose and increased insulin concentrations when administered prior to a glucose challenge. |
| 683 | 19026698 | Insulin sensitivity, circulating triglycerides and resistin levels were unchanged by the treatment regimen, but plasma adiponectin levels increased. |
| 684 | 19026698 | These data indicate that prolonged activation of the GIP receptor with GIP[mPEG] counters aspects of impaired beta-cell function and age-related glucose intolerance. |
| 685 | 19026698 | Prolonged GIP receptor activation using stable mini-PEGylated GIP improves glucose homeostasis and beta-cell function in age-related glucose intolerance. |
| 686 | 19026698 | GIP[mPEG] decreased glucose and increased insulin concentrations when administered prior to a glucose challenge. |
| 687 | 19026698 | Insulin sensitivity, circulating triglycerides and resistin levels were unchanged by the treatment regimen, but plasma adiponectin levels increased. |
| 688 | 19026698 | These data indicate that prolonged activation of the GIP receptor with GIP[mPEG] counters aspects of impaired beta-cell function and age-related glucose intolerance. |
| 689 | 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. |
| 690 | 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. |
| 691 | 19533083 | Gastric inhibitory polypeptide (GIP) is a physiological gut peptide secreted from the intestinal K-cells with well documented insulin-releasing actions. |
| 692 | 19533083 | However, the GIP receptor is widely distributed in peripheral organs, including the pancreas, gut, adipose tissue, heart, adrenal cortex and brain, suggesting that it may have other functions. |
| 693 | 19533083 | The presence of functional GIP receptors on adipocytes and the key role played by GIP in lipid metabolism and fat deposition suggest a possible beneficial effect of compromised GIP action in obesity and insulin resistance. |
| 694 | 19533083 | Thus, obese diabetic animals with compromised GIP action due to peptide-based GIP receptor antagonists, small molecular weight GIP receptor antagonists, vaccination against GIP, genetic knockout of GIP receptor or targeted K-cell destruction are protected against obesity and associated metabolic disturbances. |
| 695 | 19533083 | In addition, by causing preferential oxidation of fat, blockade of GIP signalling clears triacylglycerol deposits from liver and muscle, thereby restoring mechanisms for suppression of hepatic glucose output and improving insulin sensitivity. |
| 696 | 19533083 | Gastric inhibitory polypeptide (GIP) is a physiological gut peptide secreted from the intestinal K-cells with well documented insulin-releasing actions. |
| 697 | 19533083 | However, the GIP receptor is widely distributed in peripheral organs, including the pancreas, gut, adipose tissue, heart, adrenal cortex and brain, suggesting that it may have other functions. |
| 698 | 19533083 | The presence of functional GIP receptors on adipocytes and the key role played by GIP in lipid metabolism and fat deposition suggest a possible beneficial effect of compromised GIP action in obesity and insulin resistance. |
| 699 | 19533083 | Thus, obese diabetic animals with compromised GIP action due to peptide-based GIP receptor antagonists, small molecular weight GIP receptor antagonists, vaccination against GIP, genetic knockout of GIP receptor or targeted K-cell destruction are protected against obesity and associated metabolic disturbances. |
| 700 | 19533083 | In addition, by causing preferential oxidation of fat, blockade of GIP signalling clears triacylglycerol deposits from liver and muscle, thereby restoring mechanisms for suppression of hepatic glucose output and improving insulin sensitivity. |
| 701 | 19672815 | Glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), and G protein-coupled receptor 40 (GPR40) are members of G protein-coupled receptors (GPCR) family. |
| 702 | 19672815 | The expressions of GLP-1R, GIPR, GPR40, and a nuclear transcription factor - peroxisome-proliferator activated receptor alpha (PPARalpha) - were analyzed by real-time RT-PCR and immunoblotting. |
| 703 | 19672815 | We demonstrated that the expressions of GLP-1R, GIPR, and PPARalpha were downregulated when INS-1beta cells were treated with glucose, while their expressions were upregulated when treated with metformin or AICAR. |
| 704 | 19672815 | These results indicate that glucose, metformin, and AICAR regulated the expressions of incretin receptors and PPARalpha, but not GPR40 in beta cells. |
| 705 | 19672815 | Glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), and G protein-coupled receptor 40 (GPR40) are members of G protein-coupled receptors (GPCR) family. |
| 706 | 19672815 | The expressions of GLP-1R, GIPR, GPR40, and a nuclear transcription factor - peroxisome-proliferator activated receptor alpha (PPARalpha) - were analyzed by real-time RT-PCR and immunoblotting. |
| 707 | 19672815 | We demonstrated that the expressions of GLP-1R, GIPR, and PPARalpha were downregulated when INS-1beta cells were treated with glucose, while their expressions were upregulated when treated with metformin or AICAR. |
| 708 | 19672815 | These results indicate that glucose, metformin, and AICAR regulated the expressions of incretin receptors and PPARalpha, but not GPR40 in beta cells. |
| 709 | 19672815 | Glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), and G protein-coupled receptor 40 (GPR40) are members of G protein-coupled receptors (GPCR) family. |
| 710 | 19672815 | The expressions of GLP-1R, GIPR, GPR40, and a nuclear transcription factor - peroxisome-proliferator activated receptor alpha (PPARalpha) - were analyzed by real-time RT-PCR and immunoblotting. |
| 711 | 19672815 | We demonstrated that the expressions of GLP-1R, GIPR, and PPARalpha were downregulated when INS-1beta cells were treated with glucose, while their expressions were upregulated when treated with metformin or AICAR. |
| 712 | 19672815 | These results indicate that glucose, metformin, and AICAR regulated the expressions of incretin receptors and PPARalpha, but not GPR40 in beta cells. |
| 713 | 19748067 | Therapeutic potential for GIP receptor agonists and antagonists. |
| 714 | 19748067 | Glucose-dependent insulinotropic polypeptide (GIP or gastric inhibitory polypeptide) is a 42-amino-acid hormone, secreted from the enteroendocrine K cells, which has insulin-releasing and extrapancreatic glucoregulatory actions. |
| 715 | 19748067 | Thus, GIP receptor agonists offer one of the newest classes of potential antidiabetic drug. |
| 716 | 19748067 | Strong parallels exist with the beneficial metabolic effects of Roux-en-Y gastric bypass in obese, insulin-resistant humans that surgically ablates GIP-secreting K cells. |
| 717 | 19748067 | Therapeutic potential for GIP receptor agonists and antagonists. |
| 718 | 19748067 | Glucose-dependent insulinotropic polypeptide (GIP or gastric inhibitory polypeptide) is a 42-amino-acid hormone, secreted from the enteroendocrine K cells, which has insulin-releasing and extrapancreatic glucoregulatory actions. |
| 719 | 19748067 | Thus, GIP receptor agonists offer one of the newest classes of potential antidiabetic drug. |
| 720 | 19748067 | Strong parallels exist with the beneficial metabolic effects of Roux-en-Y gastric bypass in obese, insulin-resistant humans that surgically ablates GIP-secreting K cells. |
| 721 | 20081857 | Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. |
| 722 | 20081857 | The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). |
| 723 | 20081857 | We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. |
| 724 | 20081857 | Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)). |
| 725 | 20081857 | Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. |
| 726 | 20081857 | The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). |
| 727 | 20081857 | We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. |
| 728 | 20081857 | Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)). |
| 729 | 20081857 | Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. |
| 730 | 20081857 | The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). |
| 731 | 20081857 | We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. |
| 732 | 20081857 | Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)). |
| 733 | 20446595 | GIP and GLP-1 are major incretins and secreted from K-cell and L-cell in response to meal ingestion, respectively. |
| 734 | 20446595 | GIP and GLP-1 potentiate glucose-induced insulin secretion by binding GIP receptor and GLP-1 receptor, respectively, on pancreatic beta-cell and increasing intracellular cAMP concentration (incretin effect). |
| 735 | 20446595 | GIP receptor and GLP-1 receptor are expressed in some different organs. |
| 736 | 20446595 | GIP receptor is expressed in intestine, adipose tissue, brain, adrenal gland, and bone, while GLP-1 receptor is expressed in intestine, CNS, lung, kidney and heart. |
| 737 | 20446595 | GIP and GLP-1 have not only pancreatic effect, such as potentiation of insulin secretion, but also many extrapancreatic effects. |
| 738 | 20446595 | GIP and GLP-1 are major incretins and secreted from K-cell and L-cell in response to meal ingestion, respectively. |
| 739 | 20446595 | GIP and GLP-1 potentiate glucose-induced insulin secretion by binding GIP receptor and GLP-1 receptor, respectively, on pancreatic beta-cell and increasing intracellular cAMP concentration (incretin effect). |
| 740 | 20446595 | GIP receptor and GLP-1 receptor are expressed in some different organs. |
| 741 | 20446595 | GIP receptor is expressed in intestine, adipose tissue, brain, adrenal gland, and bone, while GLP-1 receptor is expressed in intestine, CNS, lung, kidney and heart. |
| 742 | 20446595 | GIP and GLP-1 have not only pancreatic effect, such as potentiation of insulin secretion, but also many extrapancreatic effects. |
| 743 | 20446595 | GIP and GLP-1 are major incretins and secreted from K-cell and L-cell in response to meal ingestion, respectively. |
| 744 | 20446595 | GIP and GLP-1 potentiate glucose-induced insulin secretion by binding GIP receptor and GLP-1 receptor, respectively, on pancreatic beta-cell and increasing intracellular cAMP concentration (incretin effect). |
| 745 | 20446595 | GIP receptor and GLP-1 receptor are expressed in some different organs. |
| 746 | 20446595 | GIP receptor is expressed in intestine, adipose tissue, brain, adrenal gland, and bone, while GLP-1 receptor is expressed in intestine, CNS, lung, kidney and heart. |
| 747 | 20446595 | GIP and GLP-1 have not only pancreatic effect, such as potentiation of insulin secretion, but also many extrapancreatic effects. |
| 748 | 20693566 | GIP increases human adipocyte LPL expression through CREB and TORC2-mediated trans-activation of the LPL gene. |
| 749 | 20693566 | Additionally, emerging evidence suggests an important physiological role for GIP in the regulation of adipocyte metabolism. |
| 750 | 20693566 | In previous studies on the lipogenic effects of GIP, it was shown to increase adipocyte lipoprotein lipase (LPL) activity in both differentiated 3T3-L1 cells and human adipocytes through a pathway involving activation of protein kinase B (PKB)/Akt. |
| 751 | 20693566 | In the current study, we examined the effects of GIP on LPL gene expression. |
| 752 | 20693566 | GIP in the presence of insulin increased LPL gene expression in human adipocytes and LPL promoter activity in GIP receptor-expressing HEK-293 cells, and both effects were greatly reduced by the transcription inhibitor actinomycin D. |
| 753 | 20693566 | Subsequent studies established that GIP increased phosphorylation of Serine 133 in cAMP-response element binding protein (CREB) and the nuclear localization of cAMP-responsive CREB coactivator 2 (TORC2) through a pathway involving phosphatidylinositol 3-kinase (PI3-K), PKB, and AMP-activated protein kinase (AMPK). |
| 754 | 20693566 | However, in the presence of insulin, GIP failed to activate the cAMP/PKA pathway. |
| 755 | 20693566 | Knockdown of CREB and TORC2 using RNA interference reduced LPL expression, supporting a functional regulatory role. |
| 756 | 20693566 | GIP-induced phospho-CREB and TORC2 were shown to bind to a cAMP-response element (-II) site in the human LPL promoter and GIP increased protein-protein interactions of these two factors. |
| 757 | 20693566 | The lipogenic effects of GIP in the presence of insulin are therefore at least partially mediated by upregulation of adipocyte LPL gene transcription through a pathway involving PI3-K/PKB/AMPK-dependent CREB/TORC2 activation. |
| 758 | 21050845 | Prolonged GIP receptor activation improves cognitive function, hippocampal synaptic plasticity and glucose homeostasis in high-fat fed mice. |
| 759 | 21050845 | (d-Ala(2))GIP did not affect food intake or plasma insulin levels irrespective of diet. |
| 760 | 21094903 | The glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor are homologous G-protein-coupled receptors (GPCRs). |
| 761 | 21095180 | Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic β cells. |
| 762 | 21095180 | Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. |
| 763 | 21095180 | In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. |
| 764 | 21095180 | After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. |
| 765 | 21095180 | Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. |
| 766 | 21095180 | These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin-mediated pathway rather than through a GLP-1-mediated pathway. |
| 767 | 21103350 | Variants from GIPR, TCF7L2, DGKB, MADD, CRY2, GLIS3, PROX1, SLC30A8 and IGF1 are associated with glucose metabolism in the Chinese. |
| 768 | 21212092 | Glucose-dependent insulinotropic polypeptide (GIP) is a 42 amino acid hormone secreted from intestinal K-cells, which exhibits a number of actions including stimulation of insulin release. |
| 769 | 21212092 | The results reveal that sustained GIP receptor activation exerts a spectrum of beneficial metabolic effects in high-fat fed mice. |
| 770 | 21415556 | The glucose-dependent insulinotropic polypeptide (GIP) receptor was expressed at high levels in compact cells, suggesting that GIP is responsible for the development of AIMAH. |
| 771 | 21415556 | Genetic abnormalities in the MEN1, p27, and p18 genes were not found, however, the present case may provide a clue to the understanding of the etiology of MEN1 and AIMAH. |
| 772 | 21540554 | In mice, genetic deletion of the glucagon receptor (Gcgr) results in increased levels of the insulinotropic hormone glucagon-like peptide 1 (GLP-1), which may contribute to the alterations in glucose homeostasis observed in Gcgr-/- mice. |
| 773 | 21540554 | Here, we assessed the contribution of GLP-1 receptor (GLP-1R) signaling to the phenotype of Gcgr-/- mice by generating Gcgr-/-Glp1r-/- mice. |
| 774 | 21540554 | Unexpectedly, deletion of Glp1r in Gcgr-/- mice did not alter the improved oral glucose tolerance and increased insulin secretion characteristic of that genotype. |
| 775 | 21540554 | Although Gcgr-/-Glp1r-/- islets exhibited increased sensitivity to the incretin glucose-dependent insulinotropic polypeptide (GIP), mice lacking both Glp1r and the GIP receptor (Gipr) maintained preservation of the enteroinsular axis following reduction of Gcgr signaling. |
| 776 | 21540554 | Moreover, Gcgr-/-Glp1r-/- islets expressed increased levels of the cholecystokinin A receptor (Cckar) and G protein-coupled receptor 119 (Gpr119) mRNA transcripts, and Gcgr-/-Glp1r-/- mice exhibited increased sensitivity to exogenous CCK and the GPR119 agonist AR231453. |
| 777 | 21747410 | Association between the GIPR gene and the insulin level after glucose loading in schizophrenia patients treated with olanzapine. |
| 778 | 21747410 | Glucose-dependent insulinotropic polypeptide (GIP) is known to affect insulin secretion by pancreatic β cells. |
| 779 | 21747410 | Recently, a meta-analysis study reported an association between a GIP receptor (GIPR) gene polymorphism (rs10423928) and insulin secretion measured by an oral glucose tolerance test (OGTT). |
| 780 | 21747410 | We performed repeated-measures analysis of variance (ANOVA) and one-way ANOVA for the glucose and insulin levels during OGTTs in four groups divided by the GIPR gene polymorphism and cohort (schizophrenia or control). |
| 781 | 21747410 | We found significant effects of the GIPR gene and cohort on the insulin levels at 30 min. |
| 782 | 21747410 | Association between the GIPR gene and the insulin level after glucose loading in schizophrenia patients treated with olanzapine. |
| 783 | 21747410 | Glucose-dependent insulinotropic polypeptide (GIP) is known to affect insulin secretion by pancreatic β cells. |
| 784 | 21747410 | Recently, a meta-analysis study reported an association between a GIP receptor (GIPR) gene polymorphism (rs10423928) and insulin secretion measured by an oral glucose tolerance test (OGTT). |
| 785 | 21747410 | We performed repeated-measures analysis of variance (ANOVA) and one-way ANOVA for the glucose and insulin levels during OGTTs in four groups divided by the GIPR gene polymorphism and cohort (schizophrenia or control). |
| 786 | 21747410 | We found significant effects of the GIPR gene and cohort on the insulin levels at 30 min. |
| 787 | 21747410 | Association between the GIPR gene and the insulin level after glucose loading in schizophrenia patients treated with olanzapine. |
| 788 | 21747410 | Glucose-dependent insulinotropic polypeptide (GIP) is known to affect insulin secretion by pancreatic β cells. |
| 789 | 21747410 | Recently, a meta-analysis study reported an association between a GIP receptor (GIPR) gene polymorphism (rs10423928) and insulin secretion measured by an oral glucose tolerance test (OGTT). |
| 790 | 21747410 | We performed repeated-measures analysis of variance (ANOVA) and one-way ANOVA for the glucose and insulin levels during OGTTs in four groups divided by the GIPR gene polymorphism and cohort (schizophrenia or control). |
| 791 | 21747410 | We found significant effects of the GIPR gene and cohort on the insulin levels at 30 min. |
| 792 | 21747410 | Association between the GIPR gene and the insulin level after glucose loading in schizophrenia patients treated with olanzapine. |
| 793 | 21747410 | Glucose-dependent insulinotropic polypeptide (GIP) is known to affect insulin secretion by pancreatic β cells. |
| 794 | 21747410 | Recently, a meta-analysis study reported an association between a GIP receptor (GIPR) gene polymorphism (rs10423928) and insulin secretion measured by an oral glucose tolerance test (OGTT). |
| 795 | 21747410 | We performed repeated-measures analysis of variance (ANOVA) and one-way ANOVA for the glucose and insulin levels during OGTTs in four groups divided by the GIPR gene polymorphism and cohort (schizophrenia or control). |
| 796 | 21747410 | We found significant effects of the GIPR gene and cohort on the insulin levels at 30 min. |
| 797 | 21777182 | Beside the large family A (rhodopsin-like receptors) and family C GPCR (metabotropic glutamate receptors), the small family B1 GPCR (secretin-like receptors) includes important receptors such as vasoactive intestinal peptide receptors (VPAC), pituitary adenylyl cyclase activating peptide receptor (PAC1R), secretin receptor (SECR), growth hormone releasing factor receptor (GRFR), glucagon receptor (GCGR), glucagon like-peptide 1 and 2 receptors (GLPR), gastric inhibitory peptide receptor (GIPR), parathyroid hormone receptors (PTHR), calcitonin receptors (CTR) and corticotropin-releasing factor receptors (CRFR). |
| 798 | 21820006 | Two incretin hormones GLP-1 and GIP: comparison of their actions in insulin secretion and β cell preservation. |
| 799 | 21820006 | Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the two primary incretin hormones secreted from the intestine upon ingestion of glucose or nutrients to stimulate insulin secretion from pancreatic β cells. |
| 800 | 21820006 | GIP and GLP-1 exert their effects by binding to their specific receptors, the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R), which belong to the G-protein coupled receptor family. |
| 801 | 21820006 | In addition to their insulinotropic effects, GIP and GLP-1 have been shown to preserve pancreatic β cell mass by inhibiting apoptosis of β cells and enhancing their proliferation. |
| 802 | 21820006 | However, despites of plethora of rigorous studies, molecular mechanisms underlying how GIPR and GLP-1R activation leads to enhancement of glucose-dependent insulin secretion are still largely unknown. |
| 803 | 21820006 | We then try to discuss potential of GLP-1 and GIP in treatment of type 2 diabetes. |
| 804 | 21820006 | Two incretin hormones GLP-1 and GIP: comparison of their actions in insulin secretion and β cell preservation. |
| 805 | 21820006 | Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the two primary incretin hormones secreted from the intestine upon ingestion of glucose or nutrients to stimulate insulin secretion from pancreatic β cells. |
| 806 | 21820006 | GIP and GLP-1 exert their effects by binding to their specific receptors, the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R), which belong to the G-protein coupled receptor family. |
| 807 | 21820006 | In addition to their insulinotropic effects, GIP and GLP-1 have been shown to preserve pancreatic β cell mass by inhibiting apoptosis of β cells and enhancing their proliferation. |
| 808 | 21820006 | However, despites of plethora of rigorous studies, molecular mechanisms underlying how GIPR and GLP-1R activation leads to enhancement of glucose-dependent insulin secretion are still largely unknown. |
| 809 | 21820006 | We then try to discuss potential of GLP-1 and GIP in treatment of type 2 diabetes. |
| 810 | 21893952 | Incretin receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) were therefore measured in various rodent and human thyroid conditions. |
| 811 | 21893952 | In vitro GLP-1 and GIP receptor autoradiography were performed in normal thyroids, C-cell hyperplasia and medullary thyroid carcinomas in rodents. |
| 812 | 21893952 | No GLP-1 or GIP receptors are detected in normal human thyroids. |
| 813 | 21893952 | Whereas only 27% of all human medullary thyroid carcinomas express GLP-1 receptors, up to 89% express GIP receptors in a high density. |
| 814 | 21893952 | TT cells lack GLP-1 receptors but express GIP receptors. |
| 815 | 22043004 | Glucose-dependent insulinotropic polypeptide (GIP) promotes glucose-dependent insulin secretion. |
| 816 | 22043004 | Because obesity and diabetes are glucocorticoid dependent, we examined whether the effects of GIP on energy balance and glycemia are regulated by glucocorticoids using pharmacological activation of GIP receptor (GIPR) signaling with [d-Ala(2)]GIP in mice and in Y1 adrenocortical cells. |
| 817 | 22043004 | [d-Ala(2)]GIP increased murine corticosterone levels in a GIPR-dependent manner. |
| 818 | 22043004 | [d-Ala(2)]GIP increased cAMP levels, activated extracellular signalx{2013}related kinase (ERK)1/2, increased expression of steroidogenic genes, and increased neutral lipid storage in Y1GIPR cells. |
| 819 | 22043004 | Gipr(-/-) adrenal glands demonstrated a twofold upregulation of the ACTH receptor mRNA and increased sensitivity to ACTH ex vivo. |
| 820 | 22043004 | Glucose-dependent insulinotropic polypeptide (GIP) promotes glucose-dependent insulin secretion. |
| 821 | 22043004 | Because obesity and diabetes are glucocorticoid dependent, we examined whether the effects of GIP on energy balance and glycemia are regulated by glucocorticoids using pharmacological activation of GIP receptor (GIPR) signaling with [d-Ala(2)]GIP in mice and in Y1 adrenocortical cells. |
| 822 | 22043004 | [d-Ala(2)]GIP increased murine corticosterone levels in a GIPR-dependent manner. |
| 823 | 22043004 | [d-Ala(2)]GIP increased cAMP levels, activated extracellular signalx{2013}related kinase (ERK)1/2, increased expression of steroidogenic genes, and increased neutral lipid storage in Y1GIPR cells. |
| 824 | 22043004 | Gipr(-/-) adrenal glands demonstrated a twofold upregulation of the ACTH receptor mRNA and increased sensitivity to ACTH ex vivo. |
| 825 | 22043004 | Glucose-dependent insulinotropic polypeptide (GIP) promotes glucose-dependent insulin secretion. |
| 826 | 22043004 | Because obesity and diabetes are glucocorticoid dependent, we examined whether the effects of GIP on energy balance and glycemia are regulated by glucocorticoids using pharmacological activation of GIP receptor (GIPR) signaling with [d-Ala(2)]GIP in mice and in Y1 adrenocortical cells. |
| 827 | 22043004 | [d-Ala(2)]GIP increased murine corticosterone levels in a GIPR-dependent manner. |
| 828 | 22043004 | [d-Ala(2)]GIP increased cAMP levels, activated extracellular signalx{2013}related kinase (ERK)1/2, increased expression of steroidogenic genes, and increased neutral lipid storage in Y1GIPR cells. |
| 829 | 22043004 | Gipr(-/-) adrenal glands demonstrated a twofold upregulation of the ACTH receptor mRNA and increased sensitivity to ACTH ex vivo. |
| 830 | 22403172 | Through candidate gene approach, we confirmed that Pax6 controls the mRNA levels of the insulin 1 and 2, Pdx1, MafA, GLUT2, and PC1/3 genes in β-cells. |
| 831 | 22403172 | Importantly, we identified new Pax6 target genes coding for GK, Nkx6.1, cMaf, PC2, GLP-1R and GIPR which are all involved in β-cell function. |
| 832 | 22492530 | Transgenic pigs expressing a dominant-negative glucose-dependent insulinotropic polypeptide receptor (GIPR(dn)) reveal progressive deterioration of glucose control and reduction of β-cell mass, providing a unique opportunity to study metabolic changes during the prediabetic period. |
| 833 | 22581648 | GIP receptor was expressed in HUVECs. |
| 834 | 22581648 | GIP, an analogue of cyclic AMP or inhibitors of NADPH oxidase inhibited the AGE-induced reactive oxygen species (ROS) generation in HUVECs. |
| 835 | 22581648 | GLP-1 also blocked the AGE-induced increase in mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and plasminogen activator inhibitor-1 in HUVECs. |
| 836 | 22581648 | In addition, an antioxidant N-acetylcysteine mimicked the effects of GIP on RAGE and VCAM-1 gene expression in HUVECs. |
| 837 | 22581648 | Our present study suggests that GIP could block the signal pathways of AGEs in HUVECs by reducing ROS generation and subsequent RAGE expression probably via GIP receptor-cyclic AMP axis. |
| 838 | 22581648 | GIP receptor was expressed in HUVECs. |
| 839 | 22581648 | GIP, an analogue of cyclic AMP or inhibitors of NADPH oxidase inhibited the AGE-induced reactive oxygen species (ROS) generation in HUVECs. |
| 840 | 22581648 | GLP-1 also blocked the AGE-induced increase in mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and plasminogen activator inhibitor-1 in HUVECs. |
| 841 | 22581648 | In addition, an antioxidant N-acetylcysteine mimicked the effects of GIP on RAGE and VCAM-1 gene expression in HUVECs. |
| 842 | 22581648 | Our present study suggests that GIP could block the signal pathways of AGEs in HUVECs by reducing ROS generation and subsequent RAGE expression probably via GIP receptor-cyclic AMP axis. |
| 843 | 22659620 | The G protein-coupled receptors (GPCRs) for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon are emerging as targets to treat both hyperglycemia and obesity. |
| 844 | 22659620 | GIP is rapidly released from intestinal K-cells following food intake and stimulates glucose-dependent insulin secretion from β-cells and the storage of fat in adipocytes. |
| 845 | 22659620 | Both GIP receptor agonists and antagonists have been demonstrated to display therapeutic potential to treat diabetes and obesity. |
| 846 | 22659620 | Similar to GIP, GLP-1 is released from intestinal L-cells following food intake and potentiates glucose-dependent insulin secretion from β-cells. |
| 847 | 22659620 | Here we review the biology of GIP, GLP-1 and glucagon and examine the various therapeutic strategies to activate and antagonize the receptors of these peptides. |
| 848 | 22778220 | We identified in Pax6 knockdown model that genes involved in glucagon secretion such as the glucokinase (GCK), G protein-coupled receptor (GPR40), and GIP receptor (GIPR) as well as the corresponding proteins were significantly decreased whereas the insulin receptor (IR) Kir6.2/Sur1, and glucose transporter 1 genes were not affected. |
| 849 | 22778220 | We demonstrated that Pax6 directly binds and activates specific elements on the promoter region of the GPR40, GCK, and GIPR genes. |
| 850 | 22778220 | Finally, through site-directed mutagenesis experiments, we showed that disruption of Pax6 binding on the GCK, GPR40, and GIPR gene promoters led to specific decreases of their activities in the αTC1.9 glucagon-producing cell line. |
| 851 | 22778220 | Hence our results indicate that Pax6 acts on the regulation of glucagon secretion at least through the transcriptional control of GCK, GPR40, and GIPR. |
| 852 | 22778220 | We identified in Pax6 knockdown model that genes involved in glucagon secretion such as the glucokinase (GCK), G protein-coupled receptor (GPR40), and GIP receptor (GIPR) as well as the corresponding proteins were significantly decreased whereas the insulin receptor (IR) Kir6.2/Sur1, and glucose transporter 1 genes were not affected. |
| 853 | 22778220 | We demonstrated that Pax6 directly binds and activates specific elements on the promoter region of the GPR40, GCK, and GIPR genes. |
| 854 | 22778220 | Finally, through site-directed mutagenesis experiments, we showed that disruption of Pax6 binding on the GCK, GPR40, and GIPR gene promoters led to specific decreases of their activities in the αTC1.9 glucagon-producing cell line. |
| 855 | 22778220 | Hence our results indicate that Pax6 acts on the regulation of glucagon secretion at least through the transcriptional control of GCK, GPR40, and GIPR. |
| 856 | 22778220 | We identified in Pax6 knockdown model that genes involved in glucagon secretion such as the glucokinase (GCK), G protein-coupled receptor (GPR40), and GIP receptor (GIPR) as well as the corresponding proteins were significantly decreased whereas the insulin receptor (IR) Kir6.2/Sur1, and glucose transporter 1 genes were not affected. |
| 857 | 22778220 | We demonstrated that Pax6 directly binds and activates specific elements on the promoter region of the GPR40, GCK, and GIPR genes. |
| 858 | 22778220 | Finally, through site-directed mutagenesis experiments, we showed that disruption of Pax6 binding on the GCK, GPR40, and GIPR gene promoters led to specific decreases of their activities in the αTC1.9 glucagon-producing cell line. |
| 859 | 22778220 | Hence our results indicate that Pax6 acts on the regulation of glucagon secretion at least through the transcriptional control of GCK, GPR40, and GIPR. |
| 860 | 22778220 | We identified in Pax6 knockdown model that genes involved in glucagon secretion such as the glucokinase (GCK), G protein-coupled receptor (GPR40), and GIP receptor (GIPR) as well as the corresponding proteins were significantly decreased whereas the insulin receptor (IR) Kir6.2/Sur1, and glucose transporter 1 genes were not affected. |
| 861 | 22778220 | We demonstrated that Pax6 directly binds and activates specific elements on the promoter region of the GPR40, GCK, and GIPR genes. |
| 862 | 22778220 | Finally, through site-directed mutagenesis experiments, we showed that disruption of Pax6 binding on the GCK, GPR40, and GIPR gene promoters led to specific decreases of their activities in the αTC1.9 glucagon-producing cell line. |
| 863 | 22778220 | Hence our results indicate that Pax6 acts on the regulation of glucagon secretion at least through the transcriptional control of GCK, GPR40, and GIPR. |
| 864 | 22802954 | Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that potentiates glucose-stimulated insulin secretion during a meal. |
| 865 | 22802954 | Since GIP has also been shown to exert β-cell prosurvival and adipocyte lipogenic effects in rodents, both GIP receptor agonists and antagonists have been considered as potential therapeutics in type 2 diabetes (T2DM). |
| 866 | 22802954 | In contrast, although GIP Tg mice demonstrated enhanced β-cell function, resulting in improved glucose tolerance and insulin sensitivity, they exhibited reduced diet-induced obesity. |
| 867 | 22802954 | Together, these studies suggest that, in the context of over-nutrition, transgenic GIP overexpression has the potential to improve hepatic and adipocyte function as well as glucose homeostasis. |
| 868 | 22956255 | Genetic variants in GCKR, GIPR, ADCY5 and VPS13C and the risk of severe sulfonylurea-induced hypoglycaemia in patients with type 2 diabetes. |
| 869 | 23002036 | Resistin knockout mice exhibit impaired adipocyte glucose-dependent insulinotropic polypeptide receptor (GIPR) expression. |
| 870 | 23002036 | In 3T3-L1 cells, resistin was demonstrated to be a key mediator of GIP stimulation of lipoprotein lipase (LPL) activity, involving activation of protein kinase B (PKB) and reduced phosphorylation of liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK). |
| 871 | 23002036 | The current study was initiated to determine whether resistin has additional roles in GIP-regulated adipocyte functions. |
| 872 | 23002036 | Analysis of primary adipocytes isolated from Retn(-/-), Retn(+/-), and Retn(+/+) mice found that GIP stimulated the PKB/LKB1/AMPK/LPL pathway and fatty acid uptake only in Retn(+/+) adipocytes, suggesting that GIP signaling and/or GIP responsiveness were compromised in Retn(+/-) and Retn(-/-) adipocytes. |
| 873 | 23002036 | GIP receptor (GIPR) protein and mRNA were decreased in Retn(+/-) and Retn(-/-) adipocytes, but resistin treatment rescued LPL responsiveness to GIP. |
| 874 | 23002036 | In addition, genes encoding tumor necrosis factor (TNF), TNF receptor 2 (TNFR2), and the signaling proteins stress-activated protein kinase (SAPK)/Jun NH(2)-terminal kinase (JNK), were downregulated, and phosphorylated levels of SAPK/JNK/c-Jun were decreased in Retn(-/-) mice. |
| 875 | 23002036 | Chromatin immunoprecipitation assays were used to identify a 12-O-tetradecanoylphorbol-13-acetate (TPA)-response element (TRE-III) responsible for c-Jun-mediated transcriptional activation of Gipr. |
| 876 | 23002036 | Blunted GIP responsiveness in Retn(+/-) and Retn(-/-) adipocytes was therefore largely due to the greatly reduced GIPR expression associated with decreased c-Jun-mediated transcriptional activation of Gipr. |
| 877 | 23002036 | Resistin knockout mice exhibit impaired adipocyte glucose-dependent insulinotropic polypeptide receptor (GIPR) expression. |
| 878 | 23002036 | In 3T3-L1 cells, resistin was demonstrated to be a key mediator of GIP stimulation of lipoprotein lipase (LPL) activity, involving activation of protein kinase B (PKB) and reduced phosphorylation of liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK). |
| 879 | 23002036 | The current study was initiated to determine whether resistin has additional roles in GIP-regulated adipocyte functions. |
| 880 | 23002036 | Analysis of primary adipocytes isolated from Retn(-/-), Retn(+/-), and Retn(+/+) mice found that GIP stimulated the PKB/LKB1/AMPK/LPL pathway and fatty acid uptake only in Retn(+/+) adipocytes, suggesting that GIP signaling and/or GIP responsiveness were compromised in Retn(+/-) and Retn(-/-) adipocytes. |
| 881 | 23002036 | GIP receptor (GIPR) protein and mRNA were decreased in Retn(+/-) and Retn(-/-) adipocytes, but resistin treatment rescued LPL responsiveness to GIP. |
| 882 | 23002036 | In addition, genes encoding tumor necrosis factor (TNF), TNF receptor 2 (TNFR2), and the signaling proteins stress-activated protein kinase (SAPK)/Jun NH(2)-terminal kinase (JNK), were downregulated, and phosphorylated levels of SAPK/JNK/c-Jun were decreased in Retn(-/-) mice. |
| 883 | 23002036 | Chromatin immunoprecipitation assays were used to identify a 12-O-tetradecanoylphorbol-13-acetate (TPA)-response element (TRE-III) responsible for c-Jun-mediated transcriptional activation of Gipr. |
| 884 | 23002036 | Blunted GIP responsiveness in Retn(+/-) and Retn(-/-) adipocytes was therefore largely due to the greatly reduced GIPR expression associated with decreased c-Jun-mediated transcriptional activation of Gipr. |
| 885 | 23002036 | Resistin knockout mice exhibit impaired adipocyte glucose-dependent insulinotropic polypeptide receptor (GIPR) expression. |
| 886 | 23002036 | In 3T3-L1 cells, resistin was demonstrated to be a key mediator of GIP stimulation of lipoprotein lipase (LPL) activity, involving activation of protein kinase B (PKB) and reduced phosphorylation of liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK). |
| 887 | 23002036 | The current study was initiated to determine whether resistin has additional roles in GIP-regulated adipocyte functions. |
| 888 | 23002036 | Analysis of primary adipocytes isolated from Retn(-/-), Retn(+/-), and Retn(+/+) mice found that GIP stimulated the PKB/LKB1/AMPK/LPL pathway and fatty acid uptake only in Retn(+/+) adipocytes, suggesting that GIP signaling and/or GIP responsiveness were compromised in Retn(+/-) and Retn(-/-) adipocytes. |
| 889 | 23002036 | GIP receptor (GIPR) protein and mRNA were decreased in Retn(+/-) and Retn(-/-) adipocytes, but resistin treatment rescued LPL responsiveness to GIP. |
| 890 | 23002036 | In addition, genes encoding tumor necrosis factor (TNF), TNF receptor 2 (TNFR2), and the signaling proteins stress-activated protein kinase (SAPK)/Jun NH(2)-terminal kinase (JNK), were downregulated, and phosphorylated levels of SAPK/JNK/c-Jun were decreased in Retn(-/-) mice. |
| 891 | 23002036 | Chromatin immunoprecipitation assays were used to identify a 12-O-tetradecanoylphorbol-13-acetate (TPA)-response element (TRE-III) responsible for c-Jun-mediated transcriptional activation of Gipr. |
| 892 | 23002036 | Blunted GIP responsiveness in Retn(+/-) and Retn(-/-) adipocytes was therefore largely due to the greatly reduced GIPR expression associated with decreased c-Jun-mediated transcriptional activation of Gipr. |
| 893 | 23002036 | Resistin knockout mice exhibit impaired adipocyte glucose-dependent insulinotropic polypeptide receptor (GIPR) expression. |
| 894 | 23002036 | In 3T3-L1 cells, resistin was demonstrated to be a key mediator of GIP stimulation of lipoprotein lipase (LPL) activity, involving activation of protein kinase B (PKB) and reduced phosphorylation of liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK). |
| 895 | 23002036 | The current study was initiated to determine whether resistin has additional roles in GIP-regulated adipocyte functions. |
| 896 | 23002036 | Analysis of primary adipocytes isolated from Retn(-/-), Retn(+/-), and Retn(+/+) mice found that GIP stimulated the PKB/LKB1/AMPK/LPL pathway and fatty acid uptake only in Retn(+/+) adipocytes, suggesting that GIP signaling and/or GIP responsiveness were compromised in Retn(+/-) and Retn(-/-) adipocytes. |
| 897 | 23002036 | GIP receptor (GIPR) protein and mRNA were decreased in Retn(+/-) and Retn(-/-) adipocytes, but resistin treatment rescued LPL responsiveness to GIP. |
| 898 | 23002036 | In addition, genes encoding tumor necrosis factor (TNF), TNF receptor 2 (TNFR2), and the signaling proteins stress-activated protein kinase (SAPK)/Jun NH(2)-terminal kinase (JNK), were downregulated, and phosphorylated levels of SAPK/JNK/c-Jun were decreased in Retn(-/-) mice. |
| 899 | 23002036 | Chromatin immunoprecipitation assays were used to identify a 12-O-tetradecanoylphorbol-13-acetate (TPA)-response element (TRE-III) responsible for c-Jun-mediated transcriptional activation of Gipr. |
| 900 | 23002036 | Blunted GIP responsiveness in Retn(+/-) and Retn(-/-) adipocytes was therefore largely due to the greatly reduced GIPR expression associated with decreased c-Jun-mediated transcriptional activation of Gipr. |
| 901 | 23052340 | Dominant-negative glucose-dependent insulinotropic polypeptide receptor (GIPR(dn)) transgenic mice exhibit defective postnatal islet growth, develop PNDM and progressive diabetes-associated kidney lesions. |
| 902 | 23099862 | Ectopic expression of GIP in pancreatic β-cells maintains enhanced insulin secretion in mice with complete absence of proglucagon-derived peptides. |
| 903 | 23099862 | The Gcg(gfp/gfp) mice displayed improved glucose tolerance and enhanced insulin secretion, as assessed by both oral glucose tolerance test (OGTT) and intraperitoneal glucose tolerance test (IPGTT). |
| 904 | 23099862 | Responses of glucose-dependent insulinotropic polypeptide (GIP) to both oral and intraperitoneal glucose loads were unexpectedly enhanced in Gcg(gfp/gfp) mice, and immunohistochemistry localized GIP to pancreatic β-cells of Gcg(gfp/gfp) mice. |
| 905 | 23099862 | Furthermore, secretion of GIP in response to glucose was detected in isolated islets of Gcg(gfp/gfp) mice. |
| 906 | 23099862 | Blockade of GIP action in vitro and in vivo by cAMP antagonism and genetic deletion of the GIP receptor, respectively, almost completely abrogated enhanced insulin secretion in Gcg(gfp/gfp) mice. |
| 907 | 23099862 | These results indicate that ectopic GIP expression in β-cells maintains insulin secretion in the absence of proglucagon-derived peptides (PGDPs), revealing a novel compensatory mechanism for sustaining incretin hormone action in islets. |
| 908 | 23349498 | Link between GIP and osteopontin in adipose tissue and insulin resistance. |
| 909 | 23349498 | Low-grade inflammation in obesity is associated with accumulation of the macrophage-derived cytokine osteopontin (OPN) in adipose tissue and induction of local as well as systemic insulin resistance. |
| 910 | 23349498 | Since glucose-dependent insulinotropic polypeptide (GIP) is a strong stimulator of adipogenesis and may play a role in the development of obesity, we explored whether GIP directly would stimulate OPN expression in adipose tissue and thereby induce insulin resistance. |
| 911 | 23349498 | GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. |
| 912 | 23349498 | The level of OPN mRNA was higher in adipose tissue of obese individuals (0.13 ± 0.04 vs. 0.04 ± 0.01, P < 0.05) and correlated inversely with measures of insulin sensitivity (r = -0.24, P = 0.001). |
| 913 | 23349498 | A common variant of the GIP receptor (GIPR) (rs10423928) gene was associated with a lower amount of the exon 9-containing isoform required for transmembrane activity. |
| 914 | 23349498 | Carriers of the A allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. |
| 915 | 23349498 | Together, these data suggest a role for GIP not only as an incretin hormone but also as a trigger of inflammation and insulin resistance in adipose tissue. |
| 916 | 23349498 | Carriers of the GIPR rs10423928 A allele showed protective properties via reduced GIP effects. |
| 917 | 23349498 | Identification of this unprecedented link between GIP and OPN in adipose tissue might open new avenues for therapeutic interventions. |
| 918 | 23349498 | Link between GIP and osteopontin in adipose tissue and insulin resistance. |
| 919 | 23349498 | Low-grade inflammation in obesity is associated with accumulation of the macrophage-derived cytokine osteopontin (OPN) in adipose tissue and induction of local as well as systemic insulin resistance. |
| 920 | 23349498 | Since glucose-dependent insulinotropic polypeptide (GIP) is a strong stimulator of adipogenesis and may play a role in the development of obesity, we explored whether GIP directly would stimulate OPN expression in adipose tissue and thereby induce insulin resistance. |
| 921 | 23349498 | GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. |
| 922 | 23349498 | The level of OPN mRNA was higher in adipose tissue of obese individuals (0.13 ± 0.04 vs. 0.04 ± 0.01, P < 0.05) and correlated inversely with measures of insulin sensitivity (r = -0.24, P = 0.001). |
| 923 | 23349498 | A common variant of the GIP receptor (GIPR) (rs10423928) gene was associated with a lower amount of the exon 9-containing isoform required for transmembrane activity. |
| 924 | 23349498 | Carriers of the A allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. |
| 925 | 23349498 | Together, these data suggest a role for GIP not only as an incretin hormone but also as a trigger of inflammation and insulin resistance in adipose tissue. |
| 926 | 23349498 | Carriers of the GIPR rs10423928 A allele showed protective properties via reduced GIP effects. |
| 927 | 23349498 | Identification of this unprecedented link between GIP and OPN in adipose tissue might open new avenues for therapeutic interventions. |
| 928 | 23689510 | Glucose-dependent insulinotropic polypeptide (GIP) is an endogenous hormonal factor (incretin) that, upon binding to its receptor (GIPr; a class B G-protein-coupled receptor), stimulates insulin secretion by beta cells in the pancreas. |
| 929 | 23689510 | There has been a lack of potent inhibitors of the GIPr with prolonged in vivo exposure to support studies on GIP biology. |
| 930 | 23689510 | Gipg013 is a specific competitive antagonist with equally high potencies to mouse, rat, dog, and human GIP receptors with a Ki of 7 nm for the human GIPr. |
| 931 | 23689510 | Gipg013 antagonizes the GIP receptor and inhibits GIP-induced insulin secretion in vitro and in vivo. |
| 932 | 23689510 | A crystal structure of Gipg013 Fab in complex with the human GIPr extracellular domain (ECD) shows that the antibody binds through a series of hydrogen bonds from the complementarity-determining regions of Gipg013 Fab to the N-terminal α-helix of GIPr ECD as well as to residues around its highly conserved glucagon receptor subfamily recognition fold. |
| 933 | 23689510 | The antibody epitope overlaps with the GIP binding site on the GIPr ECD, ensuring competitive antagonism of the receptor. |
| 934 | 23689510 | This well characterized antagonizing antibody to the GIPr will be useful as a tool to further understand the biological roles of GIP. |
| 935 | 23689510 | Glucose-dependent insulinotropic polypeptide (GIP) is an endogenous hormonal factor (incretin) that, upon binding to its receptor (GIPr; a class B G-protein-coupled receptor), stimulates insulin secretion by beta cells in the pancreas. |
| 936 | 23689510 | There has been a lack of potent inhibitors of the GIPr with prolonged in vivo exposure to support studies on GIP biology. |
| 937 | 23689510 | Gipg013 is a specific competitive antagonist with equally high potencies to mouse, rat, dog, and human GIP receptors with a Ki of 7 nm for the human GIPr. |
| 938 | 23689510 | Gipg013 antagonizes the GIP receptor and inhibits GIP-induced insulin secretion in vitro and in vivo. |
| 939 | 23689510 | A crystal structure of Gipg013 Fab in complex with the human GIPr extracellular domain (ECD) shows that the antibody binds through a series of hydrogen bonds from the complementarity-determining regions of Gipg013 Fab to the N-terminal α-helix of GIPr ECD as well as to residues around its highly conserved glucagon receptor subfamily recognition fold. |
| 940 | 23689510 | The antibody epitope overlaps with the GIP binding site on the GIPr ECD, ensuring competitive antagonism of the receptor. |
| 941 | 23689510 | This well characterized antagonizing antibody to the GIPr will be useful as a tool to further understand the biological roles of GIP. |
| 942 | 23689510 | Glucose-dependent insulinotropic polypeptide (GIP) is an endogenous hormonal factor (incretin) that, upon binding to its receptor (GIPr; a class B G-protein-coupled receptor), stimulates insulin secretion by beta cells in the pancreas. |
| 943 | 23689510 | There has been a lack of potent inhibitors of the GIPr with prolonged in vivo exposure to support studies on GIP biology. |
| 944 | 23689510 | Gipg013 is a specific competitive antagonist with equally high potencies to mouse, rat, dog, and human GIP receptors with a Ki of 7 nm for the human GIPr. |
| 945 | 23689510 | Gipg013 antagonizes the GIP receptor and inhibits GIP-induced insulin secretion in vitro and in vivo. |
| 946 | 23689510 | A crystal structure of Gipg013 Fab in complex with the human GIPr extracellular domain (ECD) shows that the antibody binds through a series of hydrogen bonds from the complementarity-determining regions of Gipg013 Fab to the N-terminal α-helix of GIPr ECD as well as to residues around its highly conserved glucagon receptor subfamily recognition fold. |
| 947 | 23689510 | The antibody epitope overlaps with the GIP binding site on the GIPr ECD, ensuring competitive antagonism of the receptor. |
| 948 | 23689510 | This well characterized antagonizing antibody to the GIPr will be useful as a tool to further understand the biological roles of GIP. |
| 949 | 23689510 | Glucose-dependent insulinotropic polypeptide (GIP) is an endogenous hormonal factor (incretin) that, upon binding to its receptor (GIPr; a class B G-protein-coupled receptor), stimulates insulin secretion by beta cells in the pancreas. |
| 950 | 23689510 | There has been a lack of potent inhibitors of the GIPr with prolonged in vivo exposure to support studies on GIP biology. |
| 951 | 23689510 | Gipg013 is a specific competitive antagonist with equally high potencies to mouse, rat, dog, and human GIP receptors with a Ki of 7 nm for the human GIPr. |
| 952 | 23689510 | Gipg013 antagonizes the GIP receptor and inhibits GIP-induced insulin secretion in vitro and in vivo. |
| 953 | 23689510 | A crystal structure of Gipg013 Fab in complex with the human GIPr extracellular domain (ECD) shows that the antibody binds through a series of hydrogen bonds from the complementarity-determining regions of Gipg013 Fab to the N-terminal α-helix of GIPr ECD as well as to residues around its highly conserved glucagon receptor subfamily recognition fold. |
| 954 | 23689510 | The antibody epitope overlaps with the GIP binding site on the GIPr ECD, ensuring competitive antagonism of the receptor. |
| 955 | 23689510 | This well characterized antagonizing antibody to the GIPr will be useful as a tool to further understand the biological roles of GIP. |
| 956 | 23689510 | Glucose-dependent insulinotropic polypeptide (GIP) is an endogenous hormonal factor (incretin) that, upon binding to its receptor (GIPr; a class B G-protein-coupled receptor), stimulates insulin secretion by beta cells in the pancreas. |
| 957 | 23689510 | There has been a lack of potent inhibitors of the GIPr with prolonged in vivo exposure to support studies on GIP biology. |
| 958 | 23689510 | Gipg013 is a specific competitive antagonist with equally high potencies to mouse, rat, dog, and human GIP receptors with a Ki of 7 nm for the human GIPr. |
| 959 | 23689510 | Gipg013 antagonizes the GIP receptor and inhibits GIP-induced insulin secretion in vitro and in vivo. |
| 960 | 23689510 | A crystal structure of Gipg013 Fab in complex with the human GIPr extracellular domain (ECD) shows that the antibody binds through a series of hydrogen bonds from the complementarity-determining regions of Gipg013 Fab to the N-terminal α-helix of GIPr ECD as well as to residues around its highly conserved glucagon receptor subfamily recognition fold. |
| 961 | 23689510 | The antibody epitope overlaps with the GIP binding site on the GIPr ECD, ensuring competitive antagonism of the receptor. |
| 962 | 23689510 | This well characterized antagonizing antibody to the GIPr will be useful as a tool to further understand the biological roles of GIP. |
| 963 | 23689510 | Glucose-dependent insulinotropic polypeptide (GIP) is an endogenous hormonal factor (incretin) that, upon binding to its receptor (GIPr; a class B G-protein-coupled receptor), stimulates insulin secretion by beta cells in the pancreas. |
| 964 | 23689510 | There has been a lack of potent inhibitors of the GIPr with prolonged in vivo exposure to support studies on GIP biology. |
| 965 | 23689510 | Gipg013 is a specific competitive antagonist with equally high potencies to mouse, rat, dog, and human GIP receptors with a Ki of 7 nm for the human GIPr. |
| 966 | 23689510 | Gipg013 antagonizes the GIP receptor and inhibits GIP-induced insulin secretion in vitro and in vivo. |
| 967 | 23689510 | A crystal structure of Gipg013 Fab in complex with the human GIPr extracellular domain (ECD) shows that the antibody binds through a series of hydrogen bonds from the complementarity-determining regions of Gipg013 Fab to the N-terminal α-helix of GIPr ECD as well as to residues around its highly conserved glucagon receptor subfamily recognition fold. |
| 968 | 23689510 | The antibody epitope overlaps with the GIP binding site on the GIPr ECD, ensuring competitive antagonism of the receptor. |
| 969 | 23689510 | This well characterized antagonizing antibody to the GIPr will be useful as a tool to further understand the biological roles of GIP. |
| 970 | 23689510 | Glucose-dependent insulinotropic polypeptide (GIP) is an endogenous hormonal factor (incretin) that, upon binding to its receptor (GIPr; a class B G-protein-coupled receptor), stimulates insulin secretion by beta cells in the pancreas. |
| 971 | 23689510 | There has been a lack of potent inhibitors of the GIPr with prolonged in vivo exposure to support studies on GIP biology. |
| 972 | 23689510 | Gipg013 is a specific competitive antagonist with equally high potencies to mouse, rat, dog, and human GIP receptors with a Ki of 7 nm for the human GIPr. |
| 973 | 23689510 | Gipg013 antagonizes the GIP receptor and inhibits GIP-induced insulin secretion in vitro and in vivo. |
| 974 | 23689510 | A crystal structure of Gipg013 Fab in complex with the human GIPr extracellular domain (ECD) shows that the antibody binds through a series of hydrogen bonds from the complementarity-determining regions of Gipg013 Fab to the N-terminal α-helix of GIPr ECD as well as to residues around its highly conserved glucagon receptor subfamily recognition fold. |
| 975 | 23689510 | The antibody epitope overlaps with the GIP binding site on the GIPr ECD, ensuring competitive antagonism of the receptor. |
| 976 | 23689510 | This well characterized antagonizing antibody to the GIPr will be useful as a tool to further understand the biological roles of GIP. |
| 977 | 23788637 | We have used in vitro and in vivo systems to show that FoxO1, an integrator of metabolic stimuli, inhibits PPARγ expression in β-cells, thus transcription of its target genes (Pdx1, glucose-dependent insulinotropic polypeptide (GIP) receptor, and pyruvate carboxylase) that are important regulators of β-cell function, survival, and compensation. |