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Gene Information
Gene symbol: ABCC8
Gene name: ATP-binding cassette, sub-family C (CFTR/MRP), member 8
HGNC ID: 59
Synonyms: HI, PHHI, SUR1, MRP8, ABC36, HHF1, TNDM2
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 1660613 | Since the binding constant of glyburide or iodoglyburide is closely correlated with the ability of these compounds to inhibit the ATP-sensitive K+ channel, increase [Ca2+]i, and elicit insulin secretion, we have identified the Mr 140,000 protein as the sulfonylurea receptor. |
| 2 | 7716547 | Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. |
| 3 | 7716547 | The results suggest that the sulfonylurea receptor may sense changes in ATP and ADP concentration, affect KATP channel activity, and thereby modulate insulin release. |
| 4 | 7716547 | Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. |
| 5 | 7716547 | The results suggest that the sulfonylurea receptor may sense changes in ATP and ADP concentration, affect KATP channel activity, and thereby modulate insulin release. |
| 6 | 8172912 | Glimepiride is a novel sulfonylurea drug for treatment of non-insulin-dependent diabetes mellitus with higher blood sugar lowering efficacy in diabetic patients than glibenclamide raising the question whether this characteristics is in line with different binding of glimepiride and glibenclamide to the beta-cell sulfonylurea receptor. |
| 7 | 8549873 | Recent studies have shown that the beta-cell KATP channel comprises two subunits: a novel member of the inwardly rectifying K+ channel family, designated BIR and expressed at highest levels in pancreatic islets, and the sulfonylurea receptor (SUR). |
| 8 | 8549873 | The present study examined the contribution of the linked BIR and SUR genes to the development of NIDDM. |
| 9 | 8549873 | There was no evidence for linkage between these markers and NIDDM, suggesting that genetic variation in the BIR and SUR genes does not play a major role in susceptibility to NIDDM in Japanese. |
| 10 | 8549873 | Recent studies have shown that the beta-cell KATP channel comprises two subunits: a novel member of the inwardly rectifying K+ channel family, designated BIR and expressed at highest levels in pancreatic islets, and the sulfonylurea receptor (SUR). |
| 11 | 8549873 | The present study examined the contribution of the linked BIR and SUR genes to the development of NIDDM. |
| 12 | 8549873 | There was no evidence for linkage between these markers and NIDDM, suggesting that genetic variation in the BIR and SUR genes does not play a major role in susceptibility to NIDDM in Japanese. |
| 13 | 8549873 | Recent studies have shown that the beta-cell KATP channel comprises two subunits: a novel member of the inwardly rectifying K+ channel family, designated BIR and expressed at highest levels in pancreatic islets, and the sulfonylurea receptor (SUR). |
| 14 | 8549873 | The present study examined the contribution of the linked BIR and SUR genes to the development of NIDDM. |
| 15 | 8549873 | There was no evidence for linkage between these markers and NIDDM, suggesting that genetic variation in the BIR and SUR genes does not play a major role in susceptibility to NIDDM in Japanese. |
| 16 | 8593945 | Among regions with multiple potential candidates is chromosome 11, which includes the apolipoprotein C3 cluster, muscle glycogen phosphorylase, two insulin-dependent diabetes loci, the sulfonylurea receptor, and ataxia telangiectasia. |
| 17 | 8596634 | These drugs act by binding to a sulphonylurea receptor (SUR) in the pancreatic beta-cell membrane which inhibits an ATP-sensitive potassium (K-ATP) channel and thereby stimulates insulin secretion. |
| 18 | 8607800 | The ATP-sensitive potassium channel of insulin-secreting pancreatic beta-cells is a complex of Kir6.2, a member of the inwardly rectifying potassium channel superfamily, and the sulfonylurea receptor. |
| 19 | 8607800 | Co-expression of rat Kir6.2 and sulfonylurea receptor in human embryonic kidney cells generated a potassium current with the properties of the beta-cell ATP-sensitive potassium channel. |
| 20 | 8607800 | A quantitative reverse transcriptase-polymerase chain reaction assay indicated that Kir6.2 and sulfonylurea receptor mRNAs were abundantly expressed in rat islets and that expression of Kir6.2 mRNA was reduced by >70% in islets from Zucker diabetic fatty male rats, whereas there was no significant change in sulfonylurea receptor mRNA levels. |
| 21 | 8607800 | The ATP-sensitive potassium channel of insulin-secreting pancreatic beta-cells is a complex of Kir6.2, a member of the inwardly rectifying potassium channel superfamily, and the sulfonylurea receptor. |
| 22 | 8607800 | Co-expression of rat Kir6.2 and sulfonylurea receptor in human embryonic kidney cells generated a potassium current with the properties of the beta-cell ATP-sensitive potassium channel. |
| 23 | 8607800 | A quantitative reverse transcriptase-polymerase chain reaction assay indicated that Kir6.2 and sulfonylurea receptor mRNAs were abundantly expressed in rat islets and that expression of Kir6.2 mRNA was reduced by >70% in islets from Zucker diabetic fatty male rats, whereas there was no significant change in sulfonylurea receptor mRNA levels. |
| 24 | 8607800 | The ATP-sensitive potassium channel of insulin-secreting pancreatic beta-cells is a complex of Kir6.2, a member of the inwardly rectifying potassium channel superfamily, and the sulfonylurea receptor. |
| 25 | 8607800 | Co-expression of rat Kir6.2 and sulfonylurea receptor in human embryonic kidney cells generated a potassium current with the properties of the beta-cell ATP-sensitive potassium channel. |
| 26 | 8607800 | A quantitative reverse transcriptase-polymerase chain reaction assay indicated that Kir6.2 and sulfonylurea receptor mRNAs were abundantly expressed in rat islets and that expression of Kir6.2 mRNA was reduced by >70% in islets from Zucker diabetic fatty male rats, whereas there was no significant change in sulfonylurea receptor mRNA levels. |
| 27 | 8635661 | The sulfonylurea receptor (SUR) gene, now known to encode an integral component of the pancreatic beta-cell ATP-sensitive potassium channel, IKATP, was investigated as a logical candidate for this disorder. |
| 28 | 8635661 | The two nucleotide-binding fold (NBF) regions of SUR are known to be critical for normal glucose regulation of insulin secretion. |
| 29 | 8635661 | The sulfonylurea receptor (SUR) gene, now known to encode an integral component of the pancreatic beta-cell ATP-sensitive potassium channel, IKATP, was investigated as a logical candidate for this disorder. |
| 30 | 8635661 | The two nucleotide-binding fold (NBF) regions of SUR are known to be critical for normal glucose regulation of insulin secretion. |
| 31 | 8750563 | Binding of hypoglycemic sulfonylureas and their analogues to the sulfonylurea receptor in the beta-cell plasma membrane mediates closure of the ATP-sensitive K+-channel (KATP-channel) and thereby stimulation of insulin release. |
| 32 | 8750563 | The sulfonylurea receptor is a member of the traffic ATPase family with two intracellular nucleotide binding folds. |
| 33 | 8750563 | Binding of hypoglycemic sulfonylureas and their analogues to the sulfonylurea receptor in the beta-cell plasma membrane mediates closure of the ATP-sensitive K+-channel (KATP-channel) and thereby stimulation of insulin release. |
| 34 | 8750563 | The sulfonylurea receptor is a member of the traffic ATPase family with two intracellular nucleotide binding folds. |
| 35 | 8786023 | Mutations in the cytoplasmic domain of the sulphonylurea receptor (SUR) gene that disrupt the regulation of insulin secretion have been previously described. |
| 36 | 8786023 | In the present study, the potential role of genetic variation in the SUR gene has been investigated in non-insulin-dependent diabetes mellitus (NIDDM) through linkage studies with microsatellite markers tightly linked to the SUR gene. |
| 37 | 8786023 | Mutations in the cytoplasmic domain of the sulphonylurea receptor (SUR) gene that disrupt the regulation of insulin secretion have been previously described. |
| 38 | 8786023 | In the present study, the potential role of genetic variation in the SUR gene has been investigated in non-insulin-dependent diabetes mellitus (NIDDM) through linkage studies with microsatellite markers tightly linked to the SUR gene. |
| 39 | 8858347 | Using highly polymorphic microsatellite markers and a multipoint variance components method, we found evidence for linkage of plasma glucose concentration 2 hr after oral glucose administration to two regions on chromosome 11: beta-hemoglobin (HBB) and markers D11S899/D11S1324 near the sulfonylurea receptor (SUR) gene. |
| 40 | 8923011 | Together, these mutations are associated with 88% of the HI chromosomes of the patients studied. 86Rb+ efflux measurements of COSm6 cells co-expressing Kir6.2 and either wild-type or delta F1388 SUR1 revealed that the F1388 mutation abolished ATP-sensitive potassium channel (KATP) activity in intact cells. |
| 41 | 9032109 | The cloning of the gene encoding the beta-cell inward rectifier Kir6.2 (Bir), a subunit of the beta-cell KATP channel, provided the opportunity to look for mutations in this gene that might contribute to the impaired insulin secretion of NIDDM. |
| 42 | 9032109 | Pairwise allelic associations indicated significant linkage disequilibrium between the variants in Kir6.2 and between them and a nearby pancreatic beta-cell sulfonylurea receptor (SUR1) missense variant (S1370A), but these linkage disequilibria did not differ between the NIDDM and control groups. |
| 43 | 9032109 | The results of these studies thus revealed that mutations in the coding region of Kir6.2 1) were not responsible for the previously noted association of the SUR1 variants with NIDDM (Inoue H et al., Diabetes 45:825-831, 1996) and 2) did not contribute to the impaired insulin secretion characteristic of NIDDM in Caucasian patients. |
| 44 | 9059762 | Studies of genes involved in insulin secretion or insulin action have been successful to a certain extent by showing the implication of the IRS-1 gene, the Rad gene, the glucagon receptor gene, or the sulfonylurea receptor (SUR) gene (among others) in a low percentage of cases of NIDDM in particular populations. |
| 45 | 9075812 | The sulfonylurea receptor (SUR) is a key component in glucose-stimulated insulin secretion. |
| 46 | 9100595 | Persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a rare disorder due to defective negative feedback regulation of insulin secretion by low glucose levels, is often familial. |
| 47 | 9100595 | Most cases are recessively inherited, and mutations of the sulfonylurea receptor gene (SUR) or the closely linked KIR6.2 gene have been found in several families. |
| 48 | 9100595 | By preliminary linkage analysis, we tested the possibility of a dominant negative SUR or KIR6.2 mutant. |
| 49 | 9100595 | The insulin (INS) and glucokinase (GCK) genes were also tested as additional candidates. |
| 50 | 9100595 | We conclude that mutation of a gene other than SUR or KIR6.2 is responsible for the dominant PHHI in this family, and this gene cannot be INS or GCK. |
| 51 | 9100595 | Persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a rare disorder due to defective negative feedback regulation of insulin secretion by low glucose levels, is often familial. |
| 52 | 9100595 | Most cases are recessively inherited, and mutations of the sulfonylurea receptor gene (SUR) or the closely linked KIR6.2 gene have been found in several families. |
| 53 | 9100595 | By preliminary linkage analysis, we tested the possibility of a dominant negative SUR or KIR6.2 mutant. |
| 54 | 9100595 | The insulin (INS) and glucokinase (GCK) genes were also tested as additional candidates. |
| 55 | 9100595 | We conclude that mutation of a gene other than SUR or KIR6.2 is responsible for the dominant PHHI in this family, and this gene cannot be INS or GCK. |
| 56 | 9100595 | Persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a rare disorder due to defective negative feedback regulation of insulin secretion by low glucose levels, is often familial. |
| 57 | 9100595 | Most cases are recessively inherited, and mutations of the sulfonylurea receptor gene (SUR) or the closely linked KIR6.2 gene have been found in several families. |
| 58 | 9100595 | By preliminary linkage analysis, we tested the possibility of a dominant negative SUR or KIR6.2 mutant. |
| 59 | 9100595 | The insulin (INS) and glucokinase (GCK) genes were also tested as additional candidates. |
| 60 | 9100595 | We conclude that mutation of a gene other than SUR or KIR6.2 is responsible for the dominant PHHI in this family, and this gene cannot be INS or GCK. |
| 61 | 9166666 | Novel insulinoma cell lines produced by iterative engineering of GLUT2, glucokinase, and human insulin expression. |
| 62 | 9166666 | Cell lines that are further engineered to express the GLUT2 and glucokinase genes demonstrate stable expression of the three transgenes for the full lifetime of the lines produced to date (6 months to 1 year in continuous culture). |
| 63 | 9166666 | Several endogenous genes expressed in normal beta-cells, including rat insulin, amylin, sulfonylurea receptor, and glucokinase, are stably expressed in the insulinoma lines during these in vivo studies. |
| 64 | 9200660 | The 31-cM region of chromosome 11 including the obesity gene tubby and ATP-sensitive potassium channel genes, SUR1 and Kir6.2, does not contain a major susceptibility locus for NIDDM in 127 non-Hispanic white affected sibships. |
| 65 | 9326676 | The beta cell KATP channel is a complex of two proteins: Kir6.2 and SUR1. |
| 66 | 9326676 | The former is an ATP-sensitive K+-selective pore, whereas SUR1 is a channel regulator that endows Kir6.2 with sensitivity to sulfonylureas. |
| 67 | 9326676 | We have used a truncated form of Kir6.2, which expresses independently of SUR1, to show that phentolamine does not inhibit KATP channels by interacting with SUR1. |
| 68 | 9326676 | The beta cell KATP channel is a complex of two proteins: Kir6.2 and SUR1. |
| 69 | 9326676 | The former is an ATP-sensitive K+-selective pore, whereas SUR1 is a channel regulator that endows Kir6.2 with sensitivity to sulfonylureas. |
| 70 | 9326676 | We have used a truncated form of Kir6.2, which expresses independently of SUR1, to show that phentolamine does not inhibit KATP channels by interacting with SUR1. |
| 71 | 9326676 | The beta cell KATP channel is a complex of two proteins: Kir6.2 and SUR1. |
| 72 | 9326676 | The former is an ATP-sensitive K+-selective pore, whereas SUR1 is a channel regulator that endows Kir6.2 with sensitivity to sulfonylureas. |
| 73 | 9326676 | We have used a truncated form of Kir6.2, which expresses independently of SUR1, to show that phentolamine does not inhibit KATP channels by interacting with SUR1. |
| 74 | 9356020 | These channels comprise the sulfonylurea receptor (SUR1) and Kir6.2, a member of the inward rectifier K+ channel family. |
| 75 | 9356020 | A nonsense mutation, Tyr-->Stop at codon 12 (designated Y12X) was observed in the homozygous state in a single proband. 86Rb+ efflux measurements and single-channel recordings of COS-1 cells co-expressing SUR1 and either wild-type or Y12X mutant Kir6.2 proteins confirmed that K(ATP) channel activity was abolished by this nonsense mutation. |
| 76 | 9356020 | These channels comprise the sulfonylurea receptor (SUR1) and Kir6.2, a member of the inward rectifier K+ channel family. |
| 77 | 9356020 | A nonsense mutation, Tyr-->Stop at codon 12 (designated Y12X) was observed in the homozygous state in a single proband. 86Rb+ efflux measurements and single-channel recordings of COS-1 cells co-expressing SUR1 and either wild-type or Y12X mutant Kir6.2 proteins confirmed that K(ATP) channel activity was abolished by this nonsense mutation. |
| 78 | 9458709 | The molecular structure of KATP channels is thought to be a heteromultimeric (tetrameric) assembly of these complexes: Kir6.2 with SUR1 (SUR1/Kir6.2, pancreatic type), Kir6.2 with SUR2A (SUR2A/ Kir6.2, cardiac type), and Kir6.1 with SUR2B (SUR2B/Kir6.1, VSM type) [i.e., (SUR/Kir6.x)4]. |
| 79 | 9519757 | To analyze possible functional alterations, we reconstituted the mutant K(ATP) by coexpressing beta-cell inward rectifier (BIR) (Kir 6.2), a channel subunit of K(ATP), and mutant SUR1 in HEK293T and COS-7 cells. |
| 80 | 9568693 | Decreased tolbutamide-stimulated insulin secretion in healthy subjects with sequence variants in the high-affinity sulfonylurea receptor gene. |
| 81 | 9568693 | The high-affinity sulfonylurea receptor (SUR1) is, as a subunit of the ATP-sensitive potassium channel, an important regulator of insulin secretion in the pancreatic beta-cell. |
| 82 | 9568693 | The two missense variants (Asp673Asn and Ser1369Ala) and two sequence variants (ACC-->ACT, Thr759Thr and a c-->t intron variant in position -3 of the exon 16 splice acceptor site) were examined for association with NIDDM and for a possible influence on insulin and C-peptide secretion after intravenous glucose and tolbutamide loads in a random sample of unrelated, healthy, young Danish Caucasians. |
| 83 | 9568693 | Decreased tolbutamide-stimulated insulin secretion in healthy subjects with sequence variants in the high-affinity sulfonylurea receptor gene. |
| 84 | 9568693 | The high-affinity sulfonylurea receptor (SUR1) is, as a subunit of the ATP-sensitive potassium channel, an important regulator of insulin secretion in the pancreatic beta-cell. |
| 85 | 9568693 | The two missense variants (Asp673Asn and Ser1369Ala) and two sequence variants (ACC-->ACT, Thr759Thr and a c-->t intron variant in position -3 of the exon 16 splice acceptor site) were examined for association with NIDDM and for a possible influence on insulin and C-peptide secretion after intravenous glucose and tolbutamide loads in a random sample of unrelated, healthy, young Danish Caucasians. |
| 86 | 9618169 | Mutations in both the Kir6.2 and sulfonylurea receptor (SUR1) genes have been associated with the autosomal recessive form of this disorder. |
| 87 | 9648840 | The ATP-sensitive potassium channel, K(ATP) channel, a functional complex of the sulfonylurea receptor 1, SUR1, and an inward rectifier potassium channel subunit, Kir6.2, regulates insulin secretion in the pancreas. |
| 88 | 9648840 | Mutations in both the Kir6.2 and SUR1 genes are associated with persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a disorder of pancreatic beta-cell function characterized by excess insulin secretion and hypoglycemia. |
| 89 | 9648840 | We have studied the functional properties of novel SUR1 mutations identified in PHHI patients, including H125Q, N188S, F591L, T1139M, R1215Q, G1382S, and R1394H. |
| 90 | 9648840 | R1394H and deltaF1388 SUR1, a previously identified PHHI mutation, resulted in no functional channels when coexpressed with Kir6.2 in COS cells, while H125Q, N188S, F591L, T1139M, R1215Q, and G1382S SUR1 generated functional channels in the absence of ATP. |
| 91 | 9648840 | The ATP-sensitive potassium channel, K(ATP) channel, a functional complex of the sulfonylurea receptor 1, SUR1, and an inward rectifier potassium channel subunit, Kir6.2, regulates insulin secretion in the pancreas. |
| 92 | 9648840 | Mutations in both the Kir6.2 and SUR1 genes are associated with persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a disorder of pancreatic beta-cell function characterized by excess insulin secretion and hypoglycemia. |
| 93 | 9648840 | We have studied the functional properties of novel SUR1 mutations identified in PHHI patients, including H125Q, N188S, F591L, T1139M, R1215Q, G1382S, and R1394H. |
| 94 | 9648840 | R1394H and deltaF1388 SUR1, a previously identified PHHI mutation, resulted in no functional channels when coexpressed with Kir6.2 in COS cells, while H125Q, N188S, F591L, T1139M, R1215Q, and G1382S SUR1 generated functional channels in the absence of ATP. |
| 95 | 9648840 | The ATP-sensitive potassium channel, K(ATP) channel, a functional complex of the sulfonylurea receptor 1, SUR1, and an inward rectifier potassium channel subunit, Kir6.2, regulates insulin secretion in the pancreas. |
| 96 | 9648840 | Mutations in both the Kir6.2 and SUR1 genes are associated with persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a disorder of pancreatic beta-cell function characterized by excess insulin secretion and hypoglycemia. |
| 97 | 9648840 | We have studied the functional properties of novel SUR1 mutations identified in PHHI patients, including H125Q, N188S, F591L, T1139M, R1215Q, G1382S, and R1394H. |
| 98 | 9648840 | R1394H and deltaF1388 SUR1, a previously identified PHHI mutation, resulted in no functional channels when coexpressed with Kir6.2 in COS cells, while H125Q, N188S, F591L, T1139M, R1215Q, and G1382S SUR1 generated functional channels in the absence of ATP. |
| 99 | 9648840 | The ATP-sensitive potassium channel, K(ATP) channel, a functional complex of the sulfonylurea receptor 1, SUR1, and an inward rectifier potassium channel subunit, Kir6.2, regulates insulin secretion in the pancreas. |
| 100 | 9648840 | Mutations in both the Kir6.2 and SUR1 genes are associated with persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a disorder of pancreatic beta-cell function characterized by excess insulin secretion and hypoglycemia. |
| 101 | 9648840 | We have studied the functional properties of novel SUR1 mutations identified in PHHI patients, including H125Q, N188S, F591L, T1139M, R1215Q, G1382S, and R1394H. |
| 102 | 9648840 | R1394H and deltaF1388 SUR1, a previously identified PHHI mutation, resulted in no functional channels when coexpressed with Kir6.2 in COS cells, while H125Q, N188S, F591L, T1139M, R1215Q, and G1382S SUR1 generated functional channels in the absence of ATP. |
| 103 | 9703328 | Cloning of the promoters for the beta-cell ATP-sensitive K-channel subunits Kir6.2 and SUR1. |
| 104 | 9703328 | The beta-cell ATP-sensitive potassium channel (K-ATP channel), which regulates insulin secretion, is composed of two types of subunits: 1) a sulfonylurea receptor (SUR1) and 2) an inwardly rectifying potassium channel (Kir6.2). |
| 105 | 9703328 | Several E-boxes and potential Sp1 sites are present in both promoters, and the Kir6.2 upstream region contains an Alu repeat. |
| 106 | 9703328 | Cloning of the promoters for the beta-cell ATP-sensitive K-channel subunits Kir6.2 and SUR1. |
| 107 | 9703328 | The beta-cell ATP-sensitive potassium channel (K-ATP channel), which regulates insulin secretion, is composed of two types of subunits: 1) a sulfonylurea receptor (SUR1) and 2) an inwardly rectifying potassium channel (Kir6.2). |
| 108 | 9703328 | Several E-boxes and potential Sp1 sites are present in both promoters, and the Kir6.2 upstream region contains an Alu repeat. |
| 109 | 9726229 | The beta-cell and cardiac muscle K(ATP) channels have recently been cloned and shown to possess a common pore-forming subunit (Kir6.2) but different sulfonylurea receptor subunits (SUR1 and SUR2A, respectively). |
| 110 | 9726229 | We examined the mechanism underlying the tissue specificity of the sulfonylureas tolbutamide and glibenclamide, and the benzamido-derivative meglitinide, using cloned beta-cell (Kir6.2/SUR1) and cardiac (Kir6.2/SUR2A) K(ATP) channels expressed in Xenopus oocytes. |
| 111 | 9726229 | Tolbutamide inhibited Kir6.2/SUR1 (Ki approximately 5 micromol/l), but not Kir6.2/SUR2A, currents with high affinity. |
| 112 | 9726229 | Meglitinide produced high-affinity inhibition of both Kir6.2/SUR1 and Kir6.2/SUR2A currents (Kis approximately 0.3 micromol/l and approximately 0.5 micromol/l, respectively). |
| 113 | 9726229 | Glibenclamide also blocked Kir6.2/SUR1 and Kir6.2/SUR2A currents with high affinity (Kis approximately 4 nmol/l and approximately 27 nmol/l, respectively); however, only for cardiac-type K(ATP) channels was this block reversible. |
| 114 | 9726229 | Physiological concentrations of MgADP (100 micromol/l) enhanced glibenclamide inhibition of Kir6.2/SUR1 currents but reduced that of Kir6.2/SUR2A currents. |
| 115 | 9726229 | The beta-cell and cardiac muscle K(ATP) channels have recently been cloned and shown to possess a common pore-forming subunit (Kir6.2) but different sulfonylurea receptor subunits (SUR1 and SUR2A, respectively). |
| 116 | 9726229 | We examined the mechanism underlying the tissue specificity of the sulfonylureas tolbutamide and glibenclamide, and the benzamido-derivative meglitinide, using cloned beta-cell (Kir6.2/SUR1) and cardiac (Kir6.2/SUR2A) K(ATP) channels expressed in Xenopus oocytes. |
| 117 | 9726229 | Tolbutamide inhibited Kir6.2/SUR1 (Ki approximately 5 micromol/l), but not Kir6.2/SUR2A, currents with high affinity. |
| 118 | 9726229 | Meglitinide produced high-affinity inhibition of both Kir6.2/SUR1 and Kir6.2/SUR2A currents (Kis approximately 0.3 micromol/l and approximately 0.5 micromol/l, respectively). |
| 119 | 9726229 | Glibenclamide also blocked Kir6.2/SUR1 and Kir6.2/SUR2A currents with high affinity (Kis approximately 4 nmol/l and approximately 27 nmol/l, respectively); however, only for cardiac-type K(ATP) channels was this block reversible. |
| 120 | 9726229 | Physiological concentrations of MgADP (100 micromol/l) enhanced glibenclamide inhibition of Kir6.2/SUR1 currents but reduced that of Kir6.2/SUR2A currents. |
| 121 | 9726229 | The beta-cell and cardiac muscle K(ATP) channels have recently been cloned and shown to possess a common pore-forming subunit (Kir6.2) but different sulfonylurea receptor subunits (SUR1 and SUR2A, respectively). |
| 122 | 9726229 | We examined the mechanism underlying the tissue specificity of the sulfonylureas tolbutamide and glibenclamide, and the benzamido-derivative meglitinide, using cloned beta-cell (Kir6.2/SUR1) and cardiac (Kir6.2/SUR2A) K(ATP) channels expressed in Xenopus oocytes. |
| 123 | 9726229 | Tolbutamide inhibited Kir6.2/SUR1 (Ki approximately 5 micromol/l), but not Kir6.2/SUR2A, currents with high affinity. |
| 124 | 9726229 | Meglitinide produced high-affinity inhibition of both Kir6.2/SUR1 and Kir6.2/SUR2A currents (Kis approximately 0.3 micromol/l and approximately 0.5 micromol/l, respectively). |
| 125 | 9726229 | Glibenclamide also blocked Kir6.2/SUR1 and Kir6.2/SUR2A currents with high affinity (Kis approximately 4 nmol/l and approximately 27 nmol/l, respectively); however, only for cardiac-type K(ATP) channels was this block reversible. |
| 126 | 9726229 | Physiological concentrations of MgADP (100 micromol/l) enhanced glibenclamide inhibition of Kir6.2/SUR1 currents but reduced that of Kir6.2/SUR2A currents. |
| 127 | 9726229 | The beta-cell and cardiac muscle K(ATP) channels have recently been cloned and shown to possess a common pore-forming subunit (Kir6.2) but different sulfonylurea receptor subunits (SUR1 and SUR2A, respectively). |
| 128 | 9726229 | We examined the mechanism underlying the tissue specificity of the sulfonylureas tolbutamide and glibenclamide, and the benzamido-derivative meglitinide, using cloned beta-cell (Kir6.2/SUR1) and cardiac (Kir6.2/SUR2A) K(ATP) channels expressed in Xenopus oocytes. |
| 129 | 9726229 | Tolbutamide inhibited Kir6.2/SUR1 (Ki approximately 5 micromol/l), but not Kir6.2/SUR2A, currents with high affinity. |
| 130 | 9726229 | Meglitinide produced high-affinity inhibition of both Kir6.2/SUR1 and Kir6.2/SUR2A currents (Kis approximately 0.3 micromol/l and approximately 0.5 micromol/l, respectively). |
| 131 | 9726229 | Glibenclamide also blocked Kir6.2/SUR1 and Kir6.2/SUR2A currents with high affinity (Kis approximately 4 nmol/l and approximately 27 nmol/l, respectively); however, only for cardiac-type K(ATP) channels was this block reversible. |
| 132 | 9726229 | Physiological concentrations of MgADP (100 micromol/l) enhanced glibenclamide inhibition of Kir6.2/SUR1 currents but reduced that of Kir6.2/SUR2A currents. |
| 133 | 9726229 | The beta-cell and cardiac muscle K(ATP) channels have recently been cloned and shown to possess a common pore-forming subunit (Kir6.2) but different sulfonylurea receptor subunits (SUR1 and SUR2A, respectively). |
| 134 | 9726229 | We examined the mechanism underlying the tissue specificity of the sulfonylureas tolbutamide and glibenclamide, and the benzamido-derivative meglitinide, using cloned beta-cell (Kir6.2/SUR1) and cardiac (Kir6.2/SUR2A) K(ATP) channels expressed in Xenopus oocytes. |
| 135 | 9726229 | Tolbutamide inhibited Kir6.2/SUR1 (Ki approximately 5 micromol/l), but not Kir6.2/SUR2A, currents with high affinity. |
| 136 | 9726229 | Meglitinide produced high-affinity inhibition of both Kir6.2/SUR1 and Kir6.2/SUR2A currents (Kis approximately 0.3 micromol/l and approximately 0.5 micromol/l, respectively). |
| 137 | 9726229 | Glibenclamide also blocked Kir6.2/SUR1 and Kir6.2/SUR2A currents with high affinity (Kis approximately 4 nmol/l and approximately 27 nmol/l, respectively); however, only for cardiac-type K(ATP) channels was this block reversible. |
| 138 | 9726229 | Physiological concentrations of MgADP (100 micromol/l) enhanced glibenclamide inhibition of Kir6.2/SUR1 currents but reduced that of Kir6.2/SUR2A currents. |
| 139 | 9726229 | The beta-cell and cardiac muscle K(ATP) channels have recently been cloned and shown to possess a common pore-forming subunit (Kir6.2) but different sulfonylurea receptor subunits (SUR1 and SUR2A, respectively). |
| 140 | 9726229 | We examined the mechanism underlying the tissue specificity of the sulfonylureas tolbutamide and glibenclamide, and the benzamido-derivative meglitinide, using cloned beta-cell (Kir6.2/SUR1) and cardiac (Kir6.2/SUR2A) K(ATP) channels expressed in Xenopus oocytes. |
| 141 | 9726229 | Tolbutamide inhibited Kir6.2/SUR1 (Ki approximately 5 micromol/l), but not Kir6.2/SUR2A, currents with high affinity. |
| 142 | 9726229 | Meglitinide produced high-affinity inhibition of both Kir6.2/SUR1 and Kir6.2/SUR2A currents (Kis approximately 0.3 micromol/l and approximately 0.5 micromol/l, respectively). |
| 143 | 9726229 | Glibenclamide also blocked Kir6.2/SUR1 and Kir6.2/SUR2A currents with high affinity (Kis approximately 4 nmol/l and approximately 27 nmol/l, respectively); however, only for cardiac-type K(ATP) channels was this block reversible. |
| 144 | 9726229 | Physiological concentrations of MgADP (100 micromol/l) enhanced glibenclamide inhibition of Kir6.2/SUR1 currents but reduced that of Kir6.2/SUR2A currents. |
| 145 | 9756869 | Insulin secretion from pancreatic beta cells is coupled to cell metabolism through closure of ATP-sensitive potassium (KATP) channels, which comprise Kir6.2 and sulfonylurea receptor (SUR1) subunits. |
| 146 | 9756869 | We recorded macroscopic and single-channel currents from Xenopus oocytes expressing either Kir6.2/SUR1 or Kir6. 2DeltaC36 (which forms channels in the absence of SUR1). |
| 147 | 9756869 | Oleoyl-CoA (1 microM) activated both wild-type Kir6.2/SUR1 and Kir6.2DeltaC36 macroscopic currents, approximately 2-fold, by increasing the number and open probability of Kir6.2/SUR1 and Kir6.2DeltaC36 channels. |
| 148 | 9756869 | Oleoyl-CoA also impaired channel inhibition by ATP, increasing the Ki values for both Kir6.2/SUR1 and Kir6.2DeltaC36 currents by approximately 3-fold. |
| 149 | 9756869 | Insulin secretion from pancreatic beta cells is coupled to cell metabolism through closure of ATP-sensitive potassium (KATP) channels, which comprise Kir6.2 and sulfonylurea receptor (SUR1) subunits. |
| 150 | 9756869 | We recorded macroscopic and single-channel currents from Xenopus oocytes expressing either Kir6.2/SUR1 or Kir6. 2DeltaC36 (which forms channels in the absence of SUR1). |
| 151 | 9756869 | Oleoyl-CoA (1 microM) activated both wild-type Kir6.2/SUR1 and Kir6.2DeltaC36 macroscopic currents, approximately 2-fold, by increasing the number and open probability of Kir6.2/SUR1 and Kir6.2DeltaC36 channels. |
| 152 | 9756869 | Oleoyl-CoA also impaired channel inhibition by ATP, increasing the Ki values for both Kir6.2/SUR1 and Kir6.2DeltaC36 currents by approximately 3-fold. |
| 153 | 9756869 | Insulin secretion from pancreatic beta cells is coupled to cell metabolism through closure of ATP-sensitive potassium (KATP) channels, which comprise Kir6.2 and sulfonylurea receptor (SUR1) subunits. |
| 154 | 9756869 | We recorded macroscopic and single-channel currents from Xenopus oocytes expressing either Kir6.2/SUR1 or Kir6. 2DeltaC36 (which forms channels in the absence of SUR1). |
| 155 | 9756869 | Oleoyl-CoA (1 microM) activated both wild-type Kir6.2/SUR1 and Kir6.2DeltaC36 macroscopic currents, approximately 2-fold, by increasing the number and open probability of Kir6.2/SUR1 and Kir6.2DeltaC36 channels. |
| 156 | 9756869 | Oleoyl-CoA also impaired channel inhibition by ATP, increasing the Ki values for both Kir6.2/SUR1 and Kir6.2DeltaC36 currents by approximately 3-fold. |
| 157 | 9756869 | Insulin secretion from pancreatic beta cells is coupled to cell metabolism through closure of ATP-sensitive potassium (KATP) channels, which comprise Kir6.2 and sulfonylurea receptor (SUR1) subunits. |
| 158 | 9756869 | We recorded macroscopic and single-channel currents from Xenopus oocytes expressing either Kir6.2/SUR1 or Kir6. 2DeltaC36 (which forms channels in the absence of SUR1). |
| 159 | 9756869 | Oleoyl-CoA (1 microM) activated both wild-type Kir6.2/SUR1 and Kir6.2DeltaC36 macroscopic currents, approximately 2-fold, by increasing the number and open probability of Kir6.2/SUR1 and Kir6.2DeltaC36 channels. |
| 160 | 9756869 | Oleoyl-CoA also impaired channel inhibition by ATP, increasing the Ki values for both Kir6.2/SUR1 and Kir6.2DeltaC36 currents by approximately 3-fold. |
| 161 | 9799081 | Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia. |
| 162 | 9799081 | The high-affinity sulfonylurea receptor (SUR1) gene regulates insulin secretion and may play a role in type 2 diabetes. |
| 163 | 9799081 | A silent variant in exon 31 of SUR1 (AGG-->AGA) was detected by single-strand conformational polymorphism and genotypes were determined for 396 Mexican American subjects (289 non-diabetic). |
| 164 | 9799081 | Since we have previously reported linkage between SUR1 and hyperglycemia, the present association between a SUR1 variant and hyperinsulinemia in normal individuals from a high diabetes risk ethnic group raises the possibility of primary insulin hypersecretion as an antecedent of type 2 diabetes in at least some individuals from this population. |
| 165 | 9799081 | Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia. |
| 166 | 9799081 | The high-affinity sulfonylurea receptor (SUR1) gene regulates insulin secretion and may play a role in type 2 diabetes. |
| 167 | 9799081 | A silent variant in exon 31 of SUR1 (AGG-->AGA) was detected by single-strand conformational polymorphism and genotypes were determined for 396 Mexican American subjects (289 non-diabetic). |
| 168 | 9799081 | Since we have previously reported linkage between SUR1 and hyperglycemia, the present association between a SUR1 variant and hyperinsulinemia in normal individuals from a high diabetes risk ethnic group raises the possibility of primary insulin hypersecretion as an antecedent of type 2 diabetes in at least some individuals from this population. |
| 169 | 9799081 | Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia. |
| 170 | 9799081 | The high-affinity sulfonylurea receptor (SUR1) gene regulates insulin secretion and may play a role in type 2 diabetes. |
| 171 | 9799081 | A silent variant in exon 31 of SUR1 (AGG-->AGA) was detected by single-strand conformational polymorphism and genotypes were determined for 396 Mexican American subjects (289 non-diabetic). |
| 172 | 9799081 | Since we have previously reported linkage between SUR1 and hyperglycemia, the present association between a SUR1 variant and hyperinsulinemia in normal individuals from a high diabetes risk ethnic group raises the possibility of primary insulin hypersecretion as an antecedent of type 2 diabetes in at least some individuals from this population. |
| 173 | 9799081 | Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia. |
| 174 | 9799081 | The high-affinity sulfonylurea receptor (SUR1) gene regulates insulin secretion and may play a role in type 2 diabetes. |
| 175 | 9799081 | A silent variant in exon 31 of SUR1 (AGG-->AGA) was detected by single-strand conformational polymorphism and genotypes were determined for 396 Mexican American subjects (289 non-diabetic). |
| 176 | 9799081 | Since we have previously reported linkage between SUR1 and hyperglycemia, the present association between a SUR1 variant and hyperinsulinemia in normal individuals from a high diabetes risk ethnic group raises the possibility of primary insulin hypersecretion as an antecedent of type 2 diabetes in at least some individuals from this population. |
| 177 | 9813050 | The ATP-dependent potassium (KATP) channel in the pancreatic beta-cell is a complex of two proteins, the pore-forming Kir6.2 and the sulfonylurea receptor type 1 (SUR1). |
| 178 | 9885743 | Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. |
| 179 | 9885743 | Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus. |
| 180 | 10199129 | A lot of key molecules of the systems, including GLUT2, glucokinase, SUR1, Kir6.2 and CD38, have been cloned and characterized whether the mutations in these genes are responsible for the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). |
| 181 | 10204114 | The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2, a weak inward rectifier, in a 1:1 stoichiometry. |
| 182 | 10204114 | The pore of the channel is formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active channels is (SUR1/KIR6.2)4. |
| 183 | 10204114 | The single-channel conductance of the homomeric KIR6.2 channels is equivalent to SUR/KIR6.2 channels, but they differ in all other respects, including bursting behavior, pharmacological properties, sensitivity to ATP and ADP, and trafficking to the plasma membrane. |
| 184 | 10204114 | The key role KATP channel play in the regulation of insulin secretion in response to changes in glucose metabolism is underscored by the finding that a recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits that result in the loss of channel activity. |
| 185 | 10204114 | PHHI mutations have been informative on the function of SUR1 and regulation of KATP channels by adenine nucleotides. |
| 186 | 10204114 | An unexpected finding is that the inhibitory action of ATP appears to be through a site located on KIR6.2, whose affinity for ATP is modified by SUR1. |
| 187 | 10204114 | A PHHI mutation, G1479R, in the second NBF of SUR1 forms active KATP channels that respond normally to ATP, but fail to activate with MgADP. |
| 188 | 10204114 | The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2, a weak inward rectifier, in a 1:1 stoichiometry. |
| 189 | 10204114 | The pore of the channel is formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active channels is (SUR1/KIR6.2)4. |
| 190 | 10204114 | The single-channel conductance of the homomeric KIR6.2 channels is equivalent to SUR/KIR6.2 channels, but they differ in all other respects, including bursting behavior, pharmacological properties, sensitivity to ATP and ADP, and trafficking to the plasma membrane. |
| 191 | 10204114 | The key role KATP channel play in the regulation of insulin secretion in response to changes in glucose metabolism is underscored by the finding that a recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits that result in the loss of channel activity. |
| 192 | 10204114 | PHHI mutations have been informative on the function of SUR1 and regulation of KATP channels by adenine nucleotides. |
| 193 | 10204114 | An unexpected finding is that the inhibitory action of ATP appears to be through a site located on KIR6.2, whose affinity for ATP is modified by SUR1. |
| 194 | 10204114 | A PHHI mutation, G1479R, in the second NBF of SUR1 forms active KATP channels that respond normally to ATP, but fail to activate with MgADP. |
| 195 | 10204114 | The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2, a weak inward rectifier, in a 1:1 stoichiometry. |
| 196 | 10204114 | The pore of the channel is formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active channels is (SUR1/KIR6.2)4. |
| 197 | 10204114 | The single-channel conductance of the homomeric KIR6.2 channels is equivalent to SUR/KIR6.2 channels, but they differ in all other respects, including bursting behavior, pharmacological properties, sensitivity to ATP and ADP, and trafficking to the plasma membrane. |
| 198 | 10204114 | The key role KATP channel play in the regulation of insulin secretion in response to changes in glucose metabolism is underscored by the finding that a recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits that result in the loss of channel activity. |
| 199 | 10204114 | PHHI mutations have been informative on the function of SUR1 and regulation of KATP channels by adenine nucleotides. |
| 200 | 10204114 | An unexpected finding is that the inhibitory action of ATP appears to be through a site located on KIR6.2, whose affinity for ATP is modified by SUR1. |
| 201 | 10204114 | A PHHI mutation, G1479R, in the second NBF of SUR1 forms active KATP channels that respond normally to ATP, but fail to activate with MgADP. |
| 202 | 10204114 | The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2, a weak inward rectifier, in a 1:1 stoichiometry. |
| 203 | 10204114 | The pore of the channel is formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active channels is (SUR1/KIR6.2)4. |
| 204 | 10204114 | The single-channel conductance of the homomeric KIR6.2 channels is equivalent to SUR/KIR6.2 channels, but they differ in all other respects, including bursting behavior, pharmacological properties, sensitivity to ATP and ADP, and trafficking to the plasma membrane. |
| 205 | 10204114 | The key role KATP channel play in the regulation of insulin secretion in response to changes in glucose metabolism is underscored by the finding that a recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits that result in the loss of channel activity. |
| 206 | 10204114 | PHHI mutations have been informative on the function of SUR1 and regulation of KATP channels by adenine nucleotides. |
| 207 | 10204114 | An unexpected finding is that the inhibitory action of ATP appears to be through a site located on KIR6.2, whose affinity for ATP is modified by SUR1. |
| 208 | 10204114 | A PHHI mutation, G1479R, in the second NBF of SUR1 forms active KATP channels that respond normally to ATP, but fail to activate with MgADP. |
| 209 | 10204114 | The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2, a weak inward rectifier, in a 1:1 stoichiometry. |
| 210 | 10204114 | The pore of the channel is formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active channels is (SUR1/KIR6.2)4. |
| 211 | 10204114 | The single-channel conductance of the homomeric KIR6.2 channels is equivalent to SUR/KIR6.2 channels, but they differ in all other respects, including bursting behavior, pharmacological properties, sensitivity to ATP and ADP, and trafficking to the plasma membrane. |
| 212 | 10204114 | The key role KATP channel play in the regulation of insulin secretion in response to changes in glucose metabolism is underscored by the finding that a recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits that result in the loss of channel activity. |
| 213 | 10204114 | PHHI mutations have been informative on the function of SUR1 and regulation of KATP channels by adenine nucleotides. |
| 214 | 10204114 | An unexpected finding is that the inhibitory action of ATP appears to be through a site located on KIR6.2, whose affinity for ATP is modified by SUR1. |
| 215 | 10204114 | A PHHI mutation, G1479R, in the second NBF of SUR1 forms active KATP channels that respond normally to ATP, but fail to activate with MgADP. |
| 216 | 10204114 | The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2, a weak inward rectifier, in a 1:1 stoichiometry. |
| 217 | 10204114 | The pore of the channel is formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active channels is (SUR1/KIR6.2)4. |
| 218 | 10204114 | The single-channel conductance of the homomeric KIR6.2 channels is equivalent to SUR/KIR6.2 channels, but they differ in all other respects, including bursting behavior, pharmacological properties, sensitivity to ATP and ADP, and trafficking to the plasma membrane. |
| 219 | 10204114 | The key role KATP channel play in the regulation of insulin secretion in response to changes in glucose metabolism is underscored by the finding that a recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits that result in the loss of channel activity. |
| 220 | 10204114 | PHHI mutations have been informative on the function of SUR1 and regulation of KATP channels by adenine nucleotides. |
| 221 | 10204114 | An unexpected finding is that the inhibitory action of ATP appears to be through a site located on KIR6.2, whose affinity for ATP is modified by SUR1. |
| 222 | 10204114 | A PHHI mutation, G1479R, in the second NBF of SUR1 forms active KATP channels that respond normally to ATP, but fail to activate with MgADP. |
| 223 | 10322409 | Clinical profiles of the glucose regulation disorders persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) and diabetes mellitus are diametrically opposed: unregulated insulin secretion versus insulin insufficiency. |
| 224 | 10334322 | Mutations in genes encoding the ATP-regulated potassium (K(ATP)) channels of the pancreatic beta-cell (SUR1 and Kir6.2) are the major known cause of persistent hyperinsulinemic hypoglycemia of infancy (PHHI). |
| 225 | 10334322 | Haplotype analysis using polymorphic markers spanning the SUR1/Kir6.2 gene cluster confirmed linkage to the 11p region. |
| 226 | 10334322 | No K(ATP) channel activity was observed in beta-cells isolated from a homozygous patient or after coexpression of recombinant Kir6.2 and SUR1 carrying the V187D mutation. |
| 227 | 10334322 | This unique SUR1 mutation explains the majority of PHHI cases in Finland and is strongly associated with a severe form of the disease. |
| 228 | 10334322 | Mutations in genes encoding the ATP-regulated potassium (K(ATP)) channels of the pancreatic beta-cell (SUR1 and Kir6.2) are the major known cause of persistent hyperinsulinemic hypoglycemia of infancy (PHHI). |
| 229 | 10334322 | Haplotype analysis using polymorphic markers spanning the SUR1/Kir6.2 gene cluster confirmed linkage to the 11p region. |
| 230 | 10334322 | No K(ATP) channel activity was observed in beta-cells isolated from a homozygous patient or after coexpression of recombinant Kir6.2 and SUR1 carrying the V187D mutation. |
| 231 | 10334322 | This unique SUR1 mutation explains the majority of PHHI cases in Finland and is strongly associated with a severe form of the disease. |
| 232 | 10334322 | Mutations in genes encoding the ATP-regulated potassium (K(ATP)) channels of the pancreatic beta-cell (SUR1 and Kir6.2) are the major known cause of persistent hyperinsulinemic hypoglycemia of infancy (PHHI). |
| 233 | 10334322 | Haplotype analysis using polymorphic markers spanning the SUR1/Kir6.2 gene cluster confirmed linkage to the 11p region. |
| 234 | 10334322 | No K(ATP) channel activity was observed in beta-cells isolated from a homozygous patient or after coexpression of recombinant Kir6.2 and SUR1 carrying the V187D mutation. |
| 235 | 10334322 | This unique SUR1 mutation explains the majority of PHHI cases in Finland and is strongly associated with a severe form of the disease. |
| 236 | 10334322 | Mutations in genes encoding the ATP-regulated potassium (K(ATP)) channels of the pancreatic beta-cell (SUR1 and Kir6.2) are the major known cause of persistent hyperinsulinemic hypoglycemia of infancy (PHHI). |
| 237 | 10334322 | Haplotype analysis using polymorphic markers spanning the SUR1/Kir6.2 gene cluster confirmed linkage to the 11p region. |
| 238 | 10334322 | No K(ATP) channel activity was observed in beta-cells isolated from a homozygous patient or after coexpression of recombinant Kir6.2 and SUR1 carrying the V187D mutation. |
| 239 | 10334322 | This unique SUR1 mutation explains the majority of PHHI cases in Finland and is strongly associated with a severe form of the disease. |
| 240 | 10338089 | K(ATP) channel is a complex composed of at least two subunits: the sulfonylurea receptor SUR1 and Kir6.2, an inward rectifier K+ channel member. |
| 241 | 10338089 | Mutations in both subunits have been identified in patients with the autosomal recessive form of hyperinsulinism, including 28 different mutations in the SUR1 gene and two mutations in the Kir6.2 gene. |
| 242 | 10338089 | Inadequately high insulin secretion in one family with an autosomal dominant mode of inheritance is caused by a mutation in the glucokinase gene, resulting in increased affinity of the enzyme for glucose. |
| 243 | 10338089 | The new molecular approaches in PHHI give further insight into the mechanism of pancreatic beta cell insulin secretion. |
| 244 | 10338089 | K(ATP) channel is a complex composed of at least two subunits: the sulfonylurea receptor SUR1 and Kir6.2, an inward rectifier K+ channel member. |
| 245 | 10338089 | Mutations in both subunits have been identified in patients with the autosomal recessive form of hyperinsulinism, including 28 different mutations in the SUR1 gene and two mutations in the Kir6.2 gene. |
| 246 | 10338089 | Inadequately high insulin secretion in one family with an autosomal dominant mode of inheritance is caused by a mutation in the glucokinase gene, resulting in increased affinity of the enzyme for glucose. |
| 247 | 10338089 | The new molecular approaches in PHHI give further insight into the mechanism of pancreatic beta cell insulin secretion. |
| 248 | 10342826 | ATP-sensitive potassium channels (K(ATP)) are formed from four pore-forming Kir6.2 subunits complexed with four regulatory sulfonylurea receptor subunits (SUR1 in pancreatic beta-cells, SUR2A in heart). |
| 249 | 10342826 | Chimeric SURs were coexpressed with Kir6.2 in Xenopus oocytes, and macroscopic currents were measured in inside-out membrane patches. |
| 250 | 10342826 | ATP-sensitive potassium channels (K(ATP)) are formed from four pore-forming Kir6.2 subunits complexed with four regulatory sulfonylurea receptor subunits (SUR1 in pancreatic beta-cells, SUR2A in heart). |
| 251 | 10342826 | Chimeric SURs were coexpressed with Kir6.2 in Xenopus oocytes, and macroscopic currents were measured in inside-out membrane patches. |
| 252 | 10373428 | The proximal promoter region contains multiple SP1-binding sites, and cotransfection experiments of the SUR1 promoter-luciferase vector with SP1 expression vector in Drosophila SL2 cells demonstrated a stimulatory effect of SP1 on SUR1 transcriptional activity. |
| 253 | 10373428 | The mobility shift assays confirmed the interaction of the SP1 transcription factor with the proximal promoter region of the SUR1 gene. |
| 254 | 10373428 | Together, these results indicate that SP1 may mediate transcription initiation of the SUR1 gene. |
| 255 | 10373428 | SUR1 and Kir6.2 mRNA levels are down-regulated by approximately 40-50% in response to glucocorticoid treatment. |
| 256 | 10373428 | Studies of mRNA turnover demonstrate that glucocorticoids most likely decrease the transcriptional activity of both SUR1 and Kir6.2 genes since glucocorticoids failed to affect the stability of each mRNA. |
| 257 | 10373428 | Likewise, the reduction in mRNA levels was correlated with a decrease in SUR1 and Kir6.2 protein levels. |
| 258 | 10373428 | The proximal promoter region contains multiple SP1-binding sites, and cotransfection experiments of the SUR1 promoter-luciferase vector with SP1 expression vector in Drosophila SL2 cells demonstrated a stimulatory effect of SP1 on SUR1 transcriptional activity. |
| 259 | 10373428 | The mobility shift assays confirmed the interaction of the SP1 transcription factor with the proximal promoter region of the SUR1 gene. |
| 260 | 10373428 | Together, these results indicate that SP1 may mediate transcription initiation of the SUR1 gene. |
| 261 | 10373428 | SUR1 and Kir6.2 mRNA levels are down-regulated by approximately 40-50% in response to glucocorticoid treatment. |
| 262 | 10373428 | Studies of mRNA turnover demonstrate that glucocorticoids most likely decrease the transcriptional activity of both SUR1 and Kir6.2 genes since glucocorticoids failed to affect the stability of each mRNA. |
| 263 | 10373428 | Likewise, the reduction in mRNA levels was correlated with a decrease in SUR1 and Kir6.2 protein levels. |
| 264 | 10373428 | The proximal promoter region contains multiple SP1-binding sites, and cotransfection experiments of the SUR1 promoter-luciferase vector with SP1 expression vector in Drosophila SL2 cells demonstrated a stimulatory effect of SP1 on SUR1 transcriptional activity. |
| 265 | 10373428 | The mobility shift assays confirmed the interaction of the SP1 transcription factor with the proximal promoter region of the SUR1 gene. |
| 266 | 10373428 | Together, these results indicate that SP1 may mediate transcription initiation of the SUR1 gene. |
| 267 | 10373428 | SUR1 and Kir6.2 mRNA levels are down-regulated by approximately 40-50% in response to glucocorticoid treatment. |
| 268 | 10373428 | Studies of mRNA turnover demonstrate that glucocorticoids most likely decrease the transcriptional activity of both SUR1 and Kir6.2 genes since glucocorticoids failed to affect the stability of each mRNA. |
| 269 | 10373428 | Likewise, the reduction in mRNA levels was correlated with a decrease in SUR1 and Kir6.2 protein levels. |
| 270 | 10373428 | The proximal promoter region contains multiple SP1-binding sites, and cotransfection experiments of the SUR1 promoter-luciferase vector with SP1 expression vector in Drosophila SL2 cells demonstrated a stimulatory effect of SP1 on SUR1 transcriptional activity. |
| 271 | 10373428 | The mobility shift assays confirmed the interaction of the SP1 transcription factor with the proximal promoter region of the SUR1 gene. |
| 272 | 10373428 | Together, these results indicate that SP1 may mediate transcription initiation of the SUR1 gene. |
| 273 | 10373428 | SUR1 and Kir6.2 mRNA levels are down-regulated by approximately 40-50% in response to glucocorticoid treatment. |
| 274 | 10373428 | Studies of mRNA turnover demonstrate that glucocorticoids most likely decrease the transcriptional activity of both SUR1 and Kir6.2 genes since glucocorticoids failed to affect the stability of each mRNA. |
| 275 | 10373428 | Likewise, the reduction in mRNA levels was correlated with a decrease in SUR1 and Kir6.2 protein levels. |
| 276 | 10373428 | The proximal promoter region contains multiple SP1-binding sites, and cotransfection experiments of the SUR1 promoter-luciferase vector with SP1 expression vector in Drosophila SL2 cells demonstrated a stimulatory effect of SP1 on SUR1 transcriptional activity. |
| 277 | 10373428 | The mobility shift assays confirmed the interaction of the SP1 transcription factor with the proximal promoter region of the SUR1 gene. |
| 278 | 10373428 | Together, these results indicate that SP1 may mediate transcription initiation of the SUR1 gene. |
| 279 | 10373428 | SUR1 and Kir6.2 mRNA levels are down-regulated by approximately 40-50% in response to glucocorticoid treatment. |
| 280 | 10373428 | Studies of mRNA turnover demonstrate that glucocorticoids most likely decrease the transcriptional activity of both SUR1 and Kir6.2 genes since glucocorticoids failed to affect the stability of each mRNA. |
| 281 | 10373428 | Likewise, the reduction in mRNA levels was correlated with a decrease in SUR1 and Kir6.2 protein levels. |
| 282 | 10373428 | The proximal promoter region contains multiple SP1-binding sites, and cotransfection experiments of the SUR1 promoter-luciferase vector with SP1 expression vector in Drosophila SL2 cells demonstrated a stimulatory effect of SP1 on SUR1 transcriptional activity. |
| 283 | 10373428 | The mobility shift assays confirmed the interaction of the SP1 transcription factor with the proximal promoter region of the SUR1 gene. |
| 284 | 10373428 | Together, these results indicate that SP1 may mediate transcription initiation of the SUR1 gene. |
| 285 | 10373428 | SUR1 and Kir6.2 mRNA levels are down-regulated by approximately 40-50% in response to glucocorticoid treatment. |
| 286 | 10373428 | Studies of mRNA turnover demonstrate that glucocorticoids most likely decrease the transcriptional activity of both SUR1 and Kir6.2 genes since glucocorticoids failed to affect the stability of each mRNA. |
| 287 | 10373428 | Likewise, the reduction in mRNA levels was correlated with a decrease in SUR1 and Kir6.2 protein levels. |
| 288 | 10421979 | The development of late onset non-insulin dependent diabetes mellitus (NIDDM) is due to a complicated interplay between genes and environment on one side, and the interaction between metabolic defects in various tissues including the pancreatic beta cell (decreased insulin secretion), skeletal muscle (insulin resistance), liver (increased gluconeogenesis), adipose tissue (increased lipolysis) and possibly gut incretin hormones (defective glucagon like peptide 1 (GLP1) secretion) on the other side. |
| 289 | 10421979 | Evidence for a genetic component includes the finding of a variety of metabolic defects in various tissues in non-diabetic subjects with a genetic predisposition to NIDDM, higher concordance rates for abnormal glucose tolerance including NIDDM in monozygotic compared with dizygotic twins, and the more recent demonstration of different NIDDM susceptibility genes at the sites of Insulin Receptor Substrate 1 (IRS1), the beta-3 adrenergic receptor, and the sulfonylurea receptor. |
| 290 | 10512365 | The ATP-sensitive K+ (K(ATP)) channels in MIN6 cells comprise inwardly rectifying K+ channel member Kir6.2 subunits and sulfonylurea receptor (SUR) 1 subunits. |
| 291 | 10512365 | Both SUR1 and Kir6.2 mRNA levels were not altered, but SUR1 protein was rather increased in MIN6-Glib. |
| 292 | 10512365 | The ATP-sensitive K+ (K(ATP)) channels in MIN6 cells comprise inwardly rectifying K+ channel member Kir6.2 subunits and sulfonylurea receptor (SUR) 1 subunits. |
| 293 | 10512365 | Both SUR1 and Kir6.2 mRNA levels were not altered, but SUR1 protein was rather increased in MIN6-Glib. |
| 294 | 10526167 | The mechanism of inhibition of beta-cell K(ATP) channels by sulfonylureas during treatment of non-insulin-dependent diabetes mellitus thus involves two components, drug-binding and conformational changes within SUR1 which are coupled to the pore subunit through its N-terminus and the disruption of nucleotide-dependent stimulatory effects of the regulatory subunit on the pore. |
| 295 | 10567373 | Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a neonatal disease characterized by dysregulation of insulin secretion accompanied by profound hypoglycemia. |
| 296 | 10567373 | The PHHI-derived cell line (NES2Y) exhibits insulin secretory characteristics typical of islet cells derived from these patients, i.e. they have no K(ATP) channel activity and as a consequence secrete insulin at constitutively high levels in the absence of glucose. |
| 297 | 10567373 | In addition, they exhibit impaired expression of the homeodomain transcription factor PDX1, which is a key component of the signaling pathway linking nutrient metabolism to the regulation of insulin gene expression. |
| 298 | 10567373 | To repair these defects NES2Y cells were triple-transfected with cDNAs encoding the two components of the K(ATP) channel (SUR1 and Kir6.2) and PDX1. |
| 299 | 10567373 | This approach to engineering PHHI-derived islet cells may be of use in gene therapy for PHHI and in cell engineering techniques for administering insulin for the treatment of diabetes mellitus. |
| 300 | 10615958 | To elucidate the genetic etiology of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) in the Japanese population, we conducted a polymerase chain reaction-single-strand conformation polymorphism analysis of the sulfonylurea receptor 1 (SUR1) and Kir6.2 genes in 17 Japanese PHHI patients, including a pair of siblings from a consanguineous family. |
| 301 | 10615958 | The inhibition is probably mediated through direct ATP interaction with a pore-forming subunit Kir6.2, whereas the activation is likely to be through a regulatory subunit SUR1. |
| 302 | 10615958 | To elucidate the genetic etiology of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) in the Japanese population, we conducted a polymerase chain reaction-single-strand conformation polymorphism analysis of the sulfonylurea receptor 1 (SUR1) and Kir6.2 genes in 17 Japanese PHHI patients, including a pair of siblings from a consanguineous family. |
| 303 | 10615958 | The inhibition is probably mediated through direct ATP interaction with a pore-forming subunit Kir6.2, whereas the activation is likely to be through a regulatory subunit SUR1. |
| 304 | 10866047 | Sulfonylurea receptor 1 and Kir6.2 expression in the novel human insulin-secreting cell line NES2Y. |
| 305 | 10866047 | NES2Y cells, like beta-cells isolated from the patient of origin, lack functional ATP-sensitive potassium channels (KATP) and also carry a defect in the insulin gene-regulatory transcription factor PDX1. |
| 306 | 10866047 | Here, we report that the NES2Y beta-cells that are transfected with the genes encoding the components of KATP channels in beta-cells, sulfonylurea receptor (SUR) 1 and Kir6.2, have operational KATP channels and show normal intracellular Ca2+ and secretory responses to glucose. |
| 307 | 10866047 | NES2Y beta-cells that are transfected with either Kir6.2 or SUR1 alone do not express functional KATP channels and have impaired intracellular free Ca2+ concentration-signaling responses to depolarization-dependent beta-cell agonists. |
| 308 | 10866047 | Sulfonylurea receptor 1 and Kir6.2 expression in the novel human insulin-secreting cell line NES2Y. |
| 309 | 10866047 | NES2Y cells, like beta-cells isolated from the patient of origin, lack functional ATP-sensitive potassium channels (KATP) and also carry a defect in the insulin gene-regulatory transcription factor PDX1. |
| 310 | 10866047 | Here, we report that the NES2Y beta-cells that are transfected with the genes encoding the components of KATP channels in beta-cells, sulfonylurea receptor (SUR) 1 and Kir6.2, have operational KATP channels and show normal intracellular Ca2+ and secretory responses to glucose. |
| 311 | 10866047 | NES2Y beta-cells that are transfected with either Kir6.2 or SUR1 alone do not express functional KATP channels and have impaired intracellular free Ca2+ concentration-signaling responses to depolarization-dependent beta-cell agonists. |
| 312 | 10866047 | Sulfonylurea receptor 1 and Kir6.2 expression in the novel human insulin-secreting cell line NES2Y. |
| 313 | 10866047 | NES2Y cells, like beta-cells isolated from the patient of origin, lack functional ATP-sensitive potassium channels (KATP) and also carry a defect in the insulin gene-regulatory transcription factor PDX1. |
| 314 | 10866047 | Here, we report that the NES2Y beta-cells that are transfected with the genes encoding the components of KATP channels in beta-cells, sulfonylurea receptor (SUR) 1 and Kir6.2, have operational KATP channels and show normal intracellular Ca2+ and secretory responses to glucose. |
| 315 | 10866047 | NES2Y beta-cells that are transfected with either Kir6.2 or SUR1 alone do not express functional KATP channels and have impaired intracellular free Ca2+ concentration-signaling responses to depolarization-dependent beta-cell agonists. |
| 316 | 10969823 | These channels are heteromultimers composed with a 4:4 stoichiometry of an inwardly rectifying K+ channel subunit (Kir6.2) plus a regulatory sulfonylurea receptor. |
| 317 | 10969823 | This architecture might facilitate coupling of [ATP(4-)] to insulin secretion and may protect against diabetic dysregulation resulting from heterozygous mutations in Kir6.2. |
| 318 | 11018078 | These channels consist of two types of protein subunit: the sulfonylurea receptor SUR1 and the inward rectifying potassium channel Kir6.2. |
| 319 | 11018078 | This clinical finding is in agreement with the results of heterologous coexpression studies of recombinant Kir6.2 and SUR1 carrying the E1506K mutation. |
| 320 | 11018078 | These channels consist of two types of protein subunit: the sulfonylurea receptor SUR1 and the inward rectifying potassium channel Kir6.2. |
| 321 | 11018078 | This clinical finding is in agreement with the results of heterologous coexpression studies of recombinant Kir6.2 and SUR1 carrying the E1506K mutation. |
| 322 | 11030411 | The sulfonylurea receptor (SUR1) of the pancreatic beta-cell ATP-sensitive potassium channel plays a key role in glucose-induced insulin secretion. |
| 323 | 11030411 | The A-allele of a single nucleotide polymorphism (SNP) in exon 31 of the SUR1 gene (AGG-->AGA; Arg1273Arg) has previously been shown to be associated with hyperinsulinemia in nondiabetic Mexican-American subjects. |
| 324 | 11030411 | These data reinforce the hypothesis that insulin secretion defects in T2DM might be at least partially related to allelic variations in the SUR1 gene. |
| 325 | 11030411 | The sulfonylurea receptor (SUR1) of the pancreatic beta-cell ATP-sensitive potassium channel plays a key role in glucose-induced insulin secretion. |
| 326 | 11030411 | The A-allele of a single nucleotide polymorphism (SNP) in exon 31 of the SUR1 gene (AGG-->AGA; Arg1273Arg) has previously been shown to be associated with hyperinsulinemia in nondiabetic Mexican-American subjects. |
| 327 | 11030411 | These data reinforce the hypothesis that insulin secretion defects in T2DM might be at least partially related to allelic variations in the SUR1 gene. |
| 328 | 11030411 | The sulfonylurea receptor (SUR1) of the pancreatic beta-cell ATP-sensitive potassium channel plays a key role in glucose-induced insulin secretion. |
| 329 | 11030411 | The A-allele of a single nucleotide polymorphism (SNP) in exon 31 of the SUR1 gene (AGG-->AGA; Arg1273Arg) has previously been shown to be associated with hyperinsulinemia in nondiabetic Mexican-American subjects. |
| 330 | 11030411 | These data reinforce the hypothesis that insulin secretion defects in T2DM might be at least partially related to allelic variations in the SUR1 gene. |
| 331 | 11038833 | [Sulfonylurea receptor gene polymorphism is associated with non-insulin dependent diabetes mellitus in Chinese population]. |
| 332 | 11078449 | The factors that influence functional coupling between the sulfonylurea receptor (SUR1) and Kir6.2 subunits of ATP-sensitive K+ (K+(ATP)) channels were studied in rat pancreatic beta-cells using patch clamp and microfluorometric techniques. |
| 333 | 11078449 | The modification, which may reflect functional disconnection between SUR1 and Kir6.2, is prevented by ATP and PIP2, which may act cooperatively to stabilize membrane cytoskeletons (F-actin structures). |
| 334 | 11078449 | The factors that influence functional coupling between the sulfonylurea receptor (SUR1) and Kir6.2 subunits of ATP-sensitive K+ (K+(ATP)) channels were studied in rat pancreatic beta-cells using patch clamp and microfluorometric techniques. |
| 335 | 11078449 | The modification, which may reflect functional disconnection between SUR1 and Kir6.2, is prevented by ATP and PIP2, which may act cooperatively to stabilize membrane cytoskeletons (F-actin structures). |
| 336 | 11078468 | Glibenclamide and glimepiride, on the other hand, block channels containing SUR1 and SUR2 with similar affinity. |
| 337 | 11078468 | Tolbutamide and gliclazide produce a reversible inhibition of Kir6.2/SUR1 and Kir6.2/SUR2 channels, whereas glibenclamide has a reversible effect on cardiac, but not beta-cell, K(ATP) channels. |
| 338 | 11078468 | Glibenclamide and glimepiride, on the other hand, block channels containing SUR1 and SUR2 with similar affinity. |
| 339 | 11078468 | Tolbutamide and gliclazide produce a reversible inhibition of Kir6.2/SUR1 and Kir6.2/SUR2 channels, whereas glibenclamide has a reversible effect on cardiac, but not beta-cell, K(ATP) channels. |
| 340 | 11147570 | (II) The underlying molecular mechanisms seemed to rely on beta cells on a sulfonylurea receptor protein, SURX, associated with the ATP-sensitive potassium channel (K(ATP)) and different from SUR1 for glibenclamide, and in muscle and adipose cells on: (a) the increased production of diacylglycerol and activation of protein kinase C; (b) the enhanced expression of glucose transporter isoforms; and (c) the insulin receptor-independent activation of the insulin receptor substrate/phosphatidylinositol-3-kinase pathway. |
| 341 | 11190420 | Meglitinide analogues belong to a new family of insulin secretagogues which stimulate insulin release by inhibiting ATP-sensitive potassium channels of the beta-cell membrane via binding to a receptor distinct from that of sulphonylureas (SUR1/KIR 6.2). |
| 342 | 11246895 | The high-affinity sulfonylurea receptor 1 (SUR1) plays an important role in regulating insulin secretion. |
| 343 | 11246895 | These results suggest that the T and cT allele variants are associated with lower insulin secretion parameters, particularly in female and overweight subjects, adding evidence to the role of SUR1 sequence variants in decreased insulin secretion. |
| 344 | 11246895 | The high-affinity sulfonylurea receptor 1 (SUR1) plays an important role in regulating insulin secretion. |
| 345 | 11246895 | These results suggest that the T and cT allele variants are associated with lower insulin secretion parameters, particularly in female and overweight subjects, adding evidence to the role of SUR1 sequence variants in decreased insulin secretion. |
| 346 | 11272144 | Glucose was also found to augment the actions of protein kinase C- and protein kinase A-dependent agonists in the absence of extracellular Ca2+. |
| 347 | 11272144 | These findings document the relationship between SUR1 gene defects and insulin secretion in vivo and in vitro and describe for the first time KATP channel-independent pathways of regulated insulin secretion in diseased human beta-cells. |
| 348 | 11272143 | Dysregulation of insulin secretion in children with congenital hyperinsulinism due to sulfonylurea receptor mutations. |
| 349 | 11272143 | Loss of acute insulin response to tolbutamide can identify children with diffuse SUR1 defects. |
| 350 | 11272143 | The greater response to glucose than to tolbutamide indicates that ATP-sensitive potassium (KATP) channel-independent pathways are involved in glucose-mediated insulin release in patients with diffuse SUR1 defects. |
| 351 | 11272143 | Dysregulation of insulin secretion in children with congenital hyperinsulinism due to sulfonylurea receptor mutations. |
| 352 | 11272143 | Loss of acute insulin response to tolbutamide can identify children with diffuse SUR1 defects. |
| 353 | 11272143 | The greater response to glucose than to tolbutamide indicates that ATP-sensitive potassium (KATP) channel-independent pathways are involved in glucose-mediated insulin release in patients with diffuse SUR1 defects. |
| 354 | 11272143 | Dysregulation of insulin secretion in children with congenital hyperinsulinism due to sulfonylurea receptor mutations. |
| 355 | 11272143 | Loss of acute insulin response to tolbutamide can identify children with diffuse SUR1 defects. |
| 356 | 11272143 | The greater response to glucose than to tolbutamide indicates that ATP-sensitive potassium (KATP) channel-independent pathways are involved in glucose-mediated insulin release in patients with diffuse SUR1 defects. |
| 357 | 11289470 | Role of common sequence variants in insulin secretion in familial type 2 diabetic kindreds: the sulfonylurea receptor, glucokinase, and hepatocyte nuclear factor 1alpha genes. |
| 358 | 11318841 | Association studies of variants in promoter and coding regions of beta-cell ATP-sensitive K-channel genes SUR1 and Kir6.2 with Type 2 diabetes mellitus (UKPDS 53). |
| 359 | 11336617 | Its action to augment insulin secretion requires binding to a high affinity sulfonylurea receptor, which results in closure of ATP-sensitive potassium channels in the beta-cells of the pancreas. |
| 360 | 11343328 | Impact of sulfonylurea receptor 1 genetic variability on non-insulin-dependent diabetes mellitus prevalence and treatment: a population study. |
| 361 | 11574406 | K(ATP) channels in muscle and beta-cells share a common pore-forming subunit, Kir6.2, but possess alternative sulfonylurea receptors (SURs; SUR1 in beta-cells, SUR2A in cardiac muscle, and SUR2B in smooth muscle). |
| 362 | 11574406 | Nicorandil activated Kir6.2/SUR2A and Kir6.2/SUR2B but not Kir6.2/SUR1 currents, consistent with its specificity for cardiac and smooth muscle K(ATP) channels. |
| 363 | 11574406 | K(ATP) channels in muscle and beta-cells share a common pore-forming subunit, Kir6.2, but possess alternative sulfonylurea receptors (SURs; SUR1 in beta-cells, SUR2A in cardiac muscle, and SUR2B in smooth muscle). |
| 364 | 11574406 | Nicorandil activated Kir6.2/SUR2A and Kir6.2/SUR2B but not Kir6.2/SUR1 currents, consistent with its specificity for cardiac and smooth muscle K(ATP) channels. |
| 365 | 11723059 | Most cases of hyperinsulinism of infancy (HI) are caused by mutations in either the sulfonylurea receptor-1 (SUR1) or the inward rectifying K(+) channel Kir6.2, two subunits of the beta-cell ATP-sensitive K(+) channel (K(ATP) channel). |
| 366 | 11723059 | Focal HI consists of adenomatous hyperplasia within a limited region of the pancreas, and it is caused by somatic loss of heterozygosity (LOH), including maternal Ch11p15-ter in a beta-cell precursor carrying a germ-line mutation in the paternal allele of SUR1 or Kir6.2. |
| 367 | 11723059 | Several imprinted genes are located within this chromosomal region, some of which, including p57(KIP2) and IGF-II, have been associated with the regulation of cell proliferation. |
| 368 | 11723059 | The fraction of beta-cells expressing p57(KIP2) did not vary significantly during development. beta-Cells within the focal lesions did not express p57(KIP2), whereas IGF-II staining inside focal lesions was mildly increased compared with unaffected surrounding tissue. |
| 369 | 11723059 | Most cases of hyperinsulinism of infancy (HI) are caused by mutations in either the sulfonylurea receptor-1 (SUR1) or the inward rectifying K(+) channel Kir6.2, two subunits of the beta-cell ATP-sensitive K(+) channel (K(ATP) channel). |
| 370 | 11723059 | Focal HI consists of adenomatous hyperplasia within a limited region of the pancreas, and it is caused by somatic loss of heterozygosity (LOH), including maternal Ch11p15-ter in a beta-cell precursor carrying a germ-line mutation in the paternal allele of SUR1 or Kir6.2. |
| 371 | 11723059 | Several imprinted genes are located within this chromosomal region, some of which, including p57(KIP2) and IGF-II, have been associated with the regulation of cell proliferation. |
| 372 | 11723059 | The fraction of beta-cells expressing p57(KIP2) did not vary significantly during development. beta-Cells within the focal lesions did not express p57(KIP2), whereas IGF-II staining inside focal lesions was mildly increased compared with unaffected surrounding tissue. |
| 373 | 11780755 | This signalling mechanism depends on glucose metabolism and requires the presence of specific molecules such as GLUT2, glucokinase and the K(ATP) channel subunits Kir6.2 and SUR1. |
| 374 | 11938023 | The pancreatic B-cell ATP-sensitive potassium channel (K(ATP)) is composed of two distinct subunits, an inwardly rectifying ion channel forming the pore (Kir6.2), and a regulatory subunit, namely the sulfonylurea receptor-1 (SUR1), which binds this widely used class of insulin-secreting drugs. |
| 375 | 11938023 | Mutations in the genes encoding Kir6.2 and SUR1 may result in familial persistent hyperinsulinemic hypoglycaemia of infancy, demonstrating their role in the regulation of insulin secretion. |
| 376 | 11938023 | Studies in various populations with different ethnic background provided evidence that various alleles of single nucleotide polymorphisms (SNPs) in the SUR1 gene, and to a less extent in the Kir6.2 gene, confer a significantly increased risk for the development of type 2 diabetes mellitus (T2DM). |
| 377 | 11938023 | The pancreatic B-cell ATP-sensitive potassium channel (K(ATP)) is composed of two distinct subunits, an inwardly rectifying ion channel forming the pore (Kir6.2), and a regulatory subunit, namely the sulfonylurea receptor-1 (SUR1), which binds this widely used class of insulin-secreting drugs. |
| 378 | 11938023 | Mutations in the genes encoding Kir6.2 and SUR1 may result in familial persistent hyperinsulinemic hypoglycaemia of infancy, demonstrating their role in the regulation of insulin secretion. |
| 379 | 11938023 | Studies in various populations with different ethnic background provided evidence that various alleles of single nucleotide polymorphisms (SNPs) in the SUR1 gene, and to a less extent in the Kir6.2 gene, confer a significantly increased risk for the development of type 2 diabetes mellitus (T2DM). |
| 380 | 11938023 | The pancreatic B-cell ATP-sensitive potassium channel (K(ATP)) is composed of two distinct subunits, an inwardly rectifying ion channel forming the pore (Kir6.2), and a regulatory subunit, namely the sulfonylurea receptor-1 (SUR1), which binds this widely used class of insulin-secreting drugs. |
| 381 | 11938023 | Mutations in the genes encoding Kir6.2 and SUR1 may result in familial persistent hyperinsulinemic hypoglycaemia of infancy, demonstrating their role in the regulation of insulin secretion. |
| 382 | 11938023 | Studies in various populations with different ethnic background provided evidence that various alleles of single nucleotide polymorphisms (SNPs) in the SUR1 gene, and to a less extent in the Kir6.2 gene, confer a significantly increased risk for the development of type 2 diabetes mellitus (T2DM). |
| 383 | 12031979 | The novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener. |
| 384 | 12031979 | Here, we report functional studies of the Kir6.2/SUR1 Selective PCO 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide (NNC 55-9216). |
| 385 | 12031979 | We recorded cloned K(ATP) channel currents from inside-out patches excised from Xenopus laevis oocytes heterologously expressing Kir6.2/SUR1, Kir6.2/SUR2A, or Kir6.2/SUR2B, corresponding to the beta-cell, cardiac, and smooth muscle types of the K(ATP) channel. |
| 386 | 12031979 | NNC 55-9216 reversibly activated Kir6.2/SUR1 currents (EC(50) = 16 micromol/l). |
| 387 | 12031979 | The novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener. |
| 388 | 12031979 | Here, we report functional studies of the Kir6.2/SUR1 Selective PCO 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide (NNC 55-9216). |
| 389 | 12031979 | We recorded cloned K(ATP) channel currents from inside-out patches excised from Xenopus laevis oocytes heterologously expressing Kir6.2/SUR1, Kir6.2/SUR2A, or Kir6.2/SUR2B, corresponding to the beta-cell, cardiac, and smooth muscle types of the K(ATP) channel. |
| 390 | 12031979 | NNC 55-9216 reversibly activated Kir6.2/SUR1 currents (EC(50) = 16 micromol/l). |
| 391 | 12031979 | The novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener. |
| 392 | 12031979 | Here, we report functional studies of the Kir6.2/SUR1 Selective PCO 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide (NNC 55-9216). |
| 393 | 12031979 | We recorded cloned K(ATP) channel currents from inside-out patches excised from Xenopus laevis oocytes heterologously expressing Kir6.2/SUR1, Kir6.2/SUR2A, or Kir6.2/SUR2B, corresponding to the beta-cell, cardiac, and smooth muscle types of the K(ATP) channel. |
| 394 | 12031979 | NNC 55-9216 reversibly activated Kir6.2/SUR1 currents (EC(50) = 16 micromol/l). |
| 395 | 12031979 | The novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener. |
| 396 | 12031979 | Here, we report functional studies of the Kir6.2/SUR1 Selective PCO 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide (NNC 55-9216). |
| 397 | 12031979 | We recorded cloned K(ATP) channel currents from inside-out patches excised from Xenopus laevis oocytes heterologously expressing Kir6.2/SUR1, Kir6.2/SUR2A, or Kir6.2/SUR2B, corresponding to the beta-cell, cardiac, and smooth muscle types of the K(ATP) channel. |
| 398 | 12031979 | NNC 55-9216 reversibly activated Kir6.2/SUR1 currents (EC(50) = 16 micromol/l). |
| 399 | 12046964 | Moreover, a possible mechanism to be considered is as follows: tolbutamide combines with sulfonylurea receptor; membrane depolarization is induced by a KATP channel with the signal of a sulfonylurea receptor; insulin is released. |
| 400 | 12046964 | The inhibition of insulin secretion by TPT may be caused by a glucose metabolic disorder in beta cells before the occurrence of membrane depolarization due to closed KATP channels interacting directly with a sulfonylurea receptor. |
| 401 | 12046964 | Moreover, a possible mechanism to be considered is as follows: tolbutamide combines with sulfonylurea receptor; membrane depolarization is induced by a KATP channel with the signal of a sulfonylurea receptor; insulin is released. |
| 402 | 12046964 | The inhibition of insulin secretion by TPT may be caused by a glucose metabolic disorder in beta cells before the occurrence of membrane depolarization due to closed KATP channels interacting directly with a sulfonylurea receptor. |
| 403 | 12118200 | Sulfonylurea receptor gene 16-3 polymorphism - association with sulfonylurea or insulin treatment in type 2 diabetic subjects. |
| 404 | 12124779 | Bioactive insulin was stored and then released following stimulation with arginine, peptones, and bombesin-physiological GIP secretagogues. |
| 405 | 12124779 | Like K-cells in vivo, the GIP/insulin-producing cells express the critical glucose sensing enzyme, glucokinase. |
| 406 | 12124779 | The K-cell lines also express relatively low levels of Kir 6.1, Kir 6.2, SUR1, and SUR2 suggesting secretion is independent of K(ATP) channels. |
| 407 | 12149601 | Allelic variation in exon 18 of the sulfonylurea receptor 1 (SUR1) gene, insulin secretion and insulin sensitivity in nondiabetic relatives of type 2 diabetic subjects. |
| 408 | 12196469 | RT-PCR detected the K(ATP) channel subunits Kir6.2 and SUR1 and glucokinase. |
| 409 | 12196472 | The inhibitory effect of these drugs was investigated on recombinant wild-type and mutant Kir6.2/SUR1 channels expressed in HEK293 cells. |
| 410 | 12196472 | Nateglinide and repaglinide dose-dependently inhibited whole-cell Kir6.2/SUR1 currents with half-maximal inhibitory concentration (IC(50)) values of 800 and 21 nmol/l, respectively. |
| 411 | 12196472 | Radioligand binding studies revealed a single high-affinity binding site for [(3)H]repaglinide on membranes prepared from HEK293 cells expressing wild-type (equilibrium dissociation constant [K(D)] = 0.40 nmol/l) or mutant (K(D) = 0.31 nmol/l) Kir6.2/SUR1 channels. |
| 412 | 12196472 | The inhibitory effect of these drugs was investigated on recombinant wild-type and mutant Kir6.2/SUR1 channels expressed in HEK293 cells. |
| 413 | 12196472 | Nateglinide and repaglinide dose-dependently inhibited whole-cell Kir6.2/SUR1 currents with half-maximal inhibitory concentration (IC(50)) values of 800 and 21 nmol/l, respectively. |
| 414 | 12196472 | Radioligand binding studies revealed a single high-affinity binding site for [(3)H]repaglinide on membranes prepared from HEK293 cells expressing wild-type (equilibrium dissociation constant [K(D)] = 0.40 nmol/l) or mutant (K(D) = 0.31 nmol/l) Kir6.2/SUR1 channels. |
| 415 | 12196472 | The inhibitory effect of these drugs was investigated on recombinant wild-type and mutant Kir6.2/SUR1 channels expressed in HEK293 cells. |
| 416 | 12196472 | Nateglinide and repaglinide dose-dependently inhibited whole-cell Kir6.2/SUR1 currents with half-maximal inhibitory concentration (IC(50)) values of 800 and 21 nmol/l, respectively. |
| 417 | 12196472 | Radioligand binding studies revealed a single high-affinity binding site for [(3)H]repaglinide on membranes prepared from HEK293 cells expressing wild-type (equilibrium dissociation constant [K(D)] = 0.40 nmol/l) or mutant (K(D) = 0.31 nmol/l) Kir6.2/SUR1 channels. |
| 418 | 12400064 | The four known genetic causes for inborn hyperinsulinism (mutations in the genes ABCC8, KCNJ11, GLUD1, and GCK) were excluded. |
| 419 | 12437993 | Expression of ABCB1 (MDR1, P-glycoprotein) increases with age in CD4(+) and CD8(+) T-lymphocytes indicating that P-glycoprotein may be involved in the secretion of cytokines, growth factors, and cytotoxic molecules. |
| 420 | 12437993 | Polymorphisms in the sulfonylurea receptor gene (ABCC8, SUR1) are associated with non-insulin-dependent diabetes mellitus (NIDDM). |
| 421 | 12452478 | Recent work identified the ATP-binding cassette transporter A1 (ABCA1) as the major regulator of plasma high density lipoprotein (HDL) cholesterol responsible for the removal of excess cholesterol from peripheral cells and tissues. |
| 422 | 12452478 | Here we discuss some novel aspects of the ABCA1 network: 1) the cellular pathways involved in cholesterol and phospholipid efflux, 2) regulation of ABCA1, 3) sulfonylurea receptor 1 (SUR1)- or cystic fibrosis transmembrane conductance regulator (CFTR)-like function of ABCA1, 4) interaction of the ABCA1 C-terminus with beta2-syntrophin, 5) ABCA1 modulation of the Rho GTPase Cdc42, 6) localization of ABCA1 in plasma membrane microdomains and intracellular sites, 7) differential effects of prebeta-HDL precursors on ABCA1 mediated alpha-HDL particle formation and 8) ABCA1 in platelets and its relation to phosphatidylserine-flippase activity. |
| 423 | 12453898 | Whereas the loss of ATP-sensitive K(+) channel (K(ATP) channel) activity in human pancreatic beta-cells causes severe hypoglycemia in certain forms of hyperinsulinemic hypoglycemia, similar channel loss in sulfonylurea receptor-1 (SUR1) and Kir6.2 null mice yields a milder phenotype that is characterized by normoglycemia, unless the animals are stressed. |
| 424 | 12453898 | While investigating potential compensatory mechanisms, we found that incretins, specifically glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), can increase the cAMP content of Sur1KO islets but do not potentiate glucose-stimulated insulin release. |
| 425 | 12453898 | Potentiation does not appear to require cAMP-activated protein kinase (PKA) because H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) and KT5720, inhibitors of PKA, do not affect stimulation by GLP-1, GIP, or exendin-4 in wild-type islets, although they block phosphorylation of cAMP-response element-binding protein. |
| 426 | 12453898 | The impaired incretin response in Sur1KO islets is specific; the stimulation of insulin release by other modulators, including mastoparan and activators of protein kinase C, is conserved. |
| 427 | 12475777 | Thus tolbutamide and gliclazide block channels containing SUR1 (beta-cell type), but not SUR2 (cardiac, smooth muscle types), whereas glibenclamide, glimepiride, repaglinide, and meglitinide block both types of channels. |
| 428 | 12475777 | We also clarify the mechanism by which MgADP produces an apparent increase of sulfonylurea efficacy on channels containing SUR1 (but not SUR2). |
| 429 | 12475777 | Thus tolbutamide and gliclazide block channels containing SUR1 (beta-cell type), but not SUR2 (cardiac, smooth muscle types), whereas glibenclamide, glimepiride, repaglinide, and meglitinide block both types of channels. |
| 430 | 12475777 | We also clarify the mechanism by which MgADP produces an apparent increase of sulfonylurea efficacy on channels containing SUR1 (but not SUR2). |
| 431 | 12540637 | Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. |
| 432 | 12540637 | The genes ABCC8 and KCNJ11, which encode the subunits sulfonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel (Kir6.2) of the beta-cell ATP-sensitive potassium (K(ATP)) channel, control insulin secretion. |
| 433 | 12540637 | Common polymorphisms in these genes (ABCC8 exon 16-3t/c, exon 18 T/C, KCNJ11 E23K) have been variably associated with type 2 diabetes, but no large ( approximately 2,000 subjects) case-control studies have been performed. |
| 434 | 12540637 | Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. |
| 435 | 12540637 | The genes ABCC8 and KCNJ11, which encode the subunits sulfonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel (Kir6.2) of the beta-cell ATP-sensitive potassium (K(ATP)) channel, control insulin secretion. |
| 436 | 12540637 | Common polymorphisms in these genes (ABCC8 exon 16-3t/c, exon 18 T/C, KCNJ11 E23K) have been variably associated with type 2 diabetes, but no large ( approximately 2,000 subjects) case-control studies have been performed. |
| 437 | 12540637 | Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. |
| 438 | 12540637 | The genes ABCC8 and KCNJ11, which encode the subunits sulfonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel (Kir6.2) of the beta-cell ATP-sensitive potassium (K(ATP)) channel, control insulin secretion. |
| 439 | 12540637 | Common polymorphisms in these genes (ABCC8 exon 16-3t/c, exon 18 T/C, KCNJ11 E23K) have been variably associated with type 2 diabetes, but no large ( approximately 2,000 subjects) case-control studies have been performed. |
| 440 | 12565699 | The K(ATP) channel is a hetero-octamer comprising two subunits: the pore-forming subunit Kir6.x (Kir6.1 or Kir6.2) and the regulatory subunit sulfonylurea receptor SUR (SUR1 or SUR2). |
| 441 | 12565699 | Heterologous expression of differing combinations of Kir6.1 or Kir6.2 and SUR1 or SUR2 variant (SUR2A or SUR2B) reconstitute different types of K(ATP) channels with distinct electrophysiological properties and nucleotide and pharmacological sensitivities corresponding to the various K(ATP) channels in native tissues. |
| 442 | 12565699 | The K(ATP) channel is a hetero-octamer comprising two subunits: the pore-forming subunit Kir6.x (Kir6.1 or Kir6.2) and the regulatory subunit sulfonylurea receptor SUR (SUR1 or SUR2). |
| 443 | 12565699 | Heterologous expression of differing combinations of Kir6.1 or Kir6.2 and SUR1 or SUR2 variant (SUR2A or SUR2B) reconstitute different types of K(ATP) channels with distinct electrophysiological properties and nucleotide and pharmacological sensitivities corresponding to the various K(ATP) channels in native tissues. |
| 444 | 12606521 | Paternal mutation of ATP-sensitive K(+) (K(ATP)) channel genes and loss of heterozygosity (LOH) of the 11p15 region including the maternal alleles of ABCC8, IGF2, and CDKN1C characterize the focal form of persistent hyperinsulinemic hypoglycemia of infancy (FoPHHI). |
| 445 | 12623161 | They contain two different structural subunits: an inwardly rectifying potassium channel subunit (Kir6.x) and a sulfonylurea receptor (SURX). |
| 446 | 12623161 | Kir6.2/SUR1 has a pivotal role in pancreatic insulin secretion. |
| 447 | 12623161 | Kir6.1 knockout mice exhibit sudden cardiac death due to cardiac ischemia, indicating that Kir6.1 rather than Kir6.2 is critical in the regulation of vascular tone. |
| 448 | 12623161 | This article summarizes current understanding of the physiology and pathophysiology of Kir6.1- and Kir6.2-containing K(ATP) channels. |
| 449 | 12623161 | They contain two different structural subunits: an inwardly rectifying potassium channel subunit (Kir6.x) and a sulfonylurea receptor (SURX). |
| 450 | 12623161 | Kir6.2/SUR1 has a pivotal role in pancreatic insulin secretion. |
| 451 | 12623161 | Kir6.1 knockout mice exhibit sudden cardiac death due to cardiac ischemia, indicating that Kir6.1 rather than Kir6.2 is critical in the regulation of vascular tone. |
| 452 | 12623161 | This article summarizes current understanding of the physiology and pathophysiology of Kir6.1- and Kir6.2-containing K(ATP) channels. |
| 453 | 12646233 | Six genes (met proto-oncogene, ATP-binding cassette transporter A1, fatty acid binding protein 2, LDL receptor defect C complementing, aldolase B, and sulfonylurea receptor) were shown to be associated with DM. |
| 454 | 12703060 | The analysis of the structure of the genes encoding K(ATP) channels that are made of four Kir subunits (forming the ionic pore) and four regulatory SUR subunits (that contain the binding site for antidiabetic sulfonylureas) allowed to several subclasses of those ionic channels to be described: Insulin secreting beta cells contain the SUR1/Kir 6.2 complex, while heart and skeletal muscles contain the SUR2A/Kir 6.2 set, vascular smooth muscles (such as those present in coronary arteries) have SUR2B/Kir 6.1 and nonvascular smooth muscle SUR2B/Kir 6.2. |
| 455 | 12704384 | To explore induced islet neogenesis in the liver as a strategy for the treatment of diabetes, we used helper-dependent adenovirus (HDAD) to deliver the pancreatic duodenal homeobox-1 gene (Ipf1; also known as Pdx-1) to streptozotocin (STZ)-treated diabetic mice. |
| 456 | 12704384 | The diabetes of STZ mice was partially reversed by HDAD-mediated transfer of NeuroD (Neurod), a factor downstream of Ipf1, and completely reversed by a combination of Neurod and betacellulin (Btc), without producing hepatitis. |
| 457 | 12704384 | We detected in the liver insulin and other islet-specific transcripts, including proinsulin-processing enzymes, beta-cell-specific glucokinase and sulfonylurea receptor. |
| 458 | 12704384 | Immunocytochemistry detected the presence of insulin, glucagon, pancreatic polypeptide and somatostatin-producing cells organized into islet clusters; immuno-electron microscopy showed typical insulin-containing granules. |
| 459 | 12879777 | SUR1 also enhances a physiological secretion of insulin induced by an increase of glucose concentration. |
| 460 | 12941782 | Recessive mutations of sulfonylurea receptor 1 (SUR1) and potassium inward rectifier 6.2 (Kir6.2), the two adjacent genes on chromosome 11p that comprise the beta-cell plasma membrane ATP-sensitive K(+) (K(ATP)) channels, are responsible for the most common form of congenital hyperinsulinism in children. |
| 461 | 14514634 | NN414, a SUR1/Kir6.2-selective potassium channel opener, reduces blood glucose and improves glucose tolerance in the VDF Zucker rat. |
| 462 | 14514634 | A novel potassium channel opener compound, NN414, selective for the SUR1/Kir6.2 subtype of the ATP-sensitive potassium channel, was used to examine the effect of reducing beta-cell workload in the male Vancouver diabetic fatty (VDF) Zucker rat model of mild type 2 diabetes. |
| 463 | 14514634 | NN414, a SUR1/Kir6.2-selective potassium channel opener, reduces blood glucose and improves glucose tolerance in the VDF Zucker rat. |
| 464 | 14514634 | A novel potassium channel opener compound, NN414, selective for the SUR1/Kir6.2 subtype of the ATP-sensitive potassium channel, was used to examine the effect of reducing beta-cell workload in the male Vancouver diabetic fatty (VDF) Zucker rat model of mild type 2 diabetes. |
| 465 | 14514649 | Patch-clamp experiments were performed on inside-out patches containing recombinant KATP channels (Kir6.2/SUR1) to record macroscopic currents. |
| 466 | 14514649 | The observed increase in KATP channel activity may result in multiple defects in glucose homeostasis, including impaired insulin and glucagon-like peptide-1 secretion and increased glucagon release. |
| 467 | 14596908 | Sulfonylureas such as glibenclamide are used to treat non-insulin-dependent diabetes since they bind to the sulfonylurea receptor. |
| 468 | 14707124 | The pancreatic ATP-sensitive potassium (K(ATP)) channel, a complex of four sulfonylurea receptor 1 (SUR1) and four potassium channel Kir6.2 subunits, regulates insulin secretion by linking metabolic changes to beta-cell membrane potential. |
| 469 | 14707124 | Importantly, both mutant channels rescued to the cell surface have normal ATP, MgADP, and diazoxide sensitivities, demonstrating that SUR1 harboring either the A116P or the V187D mutation is capable of associating with Kir6.2 to form functional K(ATP) channels. |
| 470 | 14707124 | The pancreatic ATP-sensitive potassium (K(ATP)) channel, a complex of four sulfonylurea receptor 1 (SUR1) and four potassium channel Kir6.2 subunits, regulates insulin secretion by linking metabolic changes to beta-cell membrane potential. |
| 471 | 14707124 | Importantly, both mutant channels rescued to the cell surface have normal ATP, MgADP, and diazoxide sensitivities, demonstrating that SUR1 harboring either the A116P or the V187D mutation is capable of associating with Kir6.2 to form functional K(ATP) channels. |
| 472 | 14728986 | The sulfonylurea receptor (SUR1 or ABCC8), the regulatory subunit of that channel, binds sulfonylurea agents and thus closes the channel and stimulates exocytosis of insulin-containing granules. alpha-Endosulfine (ENSA), has been proposed as the endogenous ligand for SUR1. |
| 473 | 14728986 | Our data do not suggest that ENSA could explain the linkage of T2DM to this region, but ENSA SNP 17 may have an important role in reducing the ability of the beta-cell to compensate for reduced insulin sensitivity, which in turn would increase the susceptibility to T2DM. |
| 474 | 14728987 | Endosulfine alpha (ENSA) is an endogenous ligand of the sulfonylurea receptor 1 (SUR1) that can stimulate insulin secretion by pancreatic beta cells. |
| 475 | 14728987 | In addition, we did not detect any significant correlation of skeletal muscle ENSA transcript levels with differences in insulin action in 49 non-diabetic subjects. |
| 476 | 14737020 | The mRNA expression levels of Kir2.1, Kir3.1, Kir6.1, Kir6.2, and sulfonylurea receptor (SUR) 2A and 2B subunits in heart and aortal smooth muscles were determined by the reverse-transcription polymerase chain reaction. |
| 477 | 14737020 | However, there are no significant expression changes of Kir2.1, Kir3.1, Kir6.1, and Kir6.2 in diabetic rats. |
| 478 | 14764798 | Induction of beta-cell rest by a Kir6.2/SUR1-selective K(ATP)-channel opener preserves beta-cell insulin stores and insulin secretion in human islets cultured at high (11 mM) glucose. |
| 479 | 15082027 | Clonal insulin-secreting BRIN-BD11 cells were used to examine effects of chronic 72-144 h exposure to the sulphonylureas tolbutamide and glibenclamide on insulin release, cellular insulin content, and mRNA levels of the Kir6.2 and SUR1 subunits of the beta-cell K(ATP) channel. |
| 480 | 15082027 | Chronic exposure to tolbutamide or glibenclamide had no effect upon transcription of the Kir6.2 or SUR1 subunits of the pancreatic beta-cell K(ATP) channel. |
| 481 | 15082027 | Clonal insulin-secreting BRIN-BD11 cells were used to examine effects of chronic 72-144 h exposure to the sulphonylureas tolbutamide and glibenclamide on insulin release, cellular insulin content, and mRNA levels of the Kir6.2 and SUR1 subunits of the beta-cell K(ATP) channel. |
| 482 | 15082027 | Chronic exposure to tolbutamide or glibenclamide had no effect upon transcription of the Kir6.2 or SUR1 subunits of the pancreatic beta-cell K(ATP) channel. |
| 483 | 15111507 | The genes for the sulfonylurea receptor (SUR1; encoded by ABCC8) and its associated islet ATP-sensitive potassium channel (Kir6.2; encoded by KCNJ11) are adjacent to one another on human chromosome 11. |
| 484 | 15111507 | We find that the E23K variant in Kir6.2 demonstrates very strong allelic association with a coding variant (A1369S) in the neighboring SUR1 gene (r(2) > 0.9) across a range of population samples, making it difficult to distinguish which gene and polymorphism in this region are most likely responsible for the reported association. |
| 485 | 15111507 | Like peroxisome proliferator-activated receptor gamma, the SUR1/Kir6.2 gene region both contributes to the inherited risk of type 2 diabetes and encodes proteins that are targets for hypoglycemic medications, providing an intriguing link between the underlying mechanism of disease and validated targets for pharmacological treatment. |
| 486 | 15111507 | The genes for the sulfonylurea receptor (SUR1; encoded by ABCC8) and its associated islet ATP-sensitive potassium channel (Kir6.2; encoded by KCNJ11) are adjacent to one another on human chromosome 11. |
| 487 | 15111507 | We find that the E23K variant in Kir6.2 demonstrates very strong allelic association with a coding variant (A1369S) in the neighboring SUR1 gene (r(2) > 0.9) across a range of population samples, making it difficult to distinguish which gene and polymorphism in this region are most likely responsible for the reported association. |
| 488 | 15111507 | Like peroxisome proliferator-activated receptor gamma, the SUR1/Kir6.2 gene region both contributes to the inherited risk of type 2 diabetes and encodes proteins that are targets for hypoglycemic medications, providing an intriguing link between the underlying mechanism of disease and validated targets for pharmacological treatment. |
| 489 | 15111507 | The genes for the sulfonylurea receptor (SUR1; encoded by ABCC8) and its associated islet ATP-sensitive potassium channel (Kir6.2; encoded by KCNJ11) are adjacent to one another on human chromosome 11. |
| 490 | 15111507 | We find that the E23K variant in Kir6.2 demonstrates very strong allelic association with a coding variant (A1369S) in the neighboring SUR1 gene (r(2) > 0.9) across a range of population samples, making it difficult to distinguish which gene and polymorphism in this region are most likely responsible for the reported association. |
| 491 | 15111507 | Like peroxisome proliferator-activated receptor gamma, the SUR1/Kir6.2 gene region both contributes to the inherited risk of type 2 diabetes and encodes proteins that are targets for hypoglycemic medications, providing an intriguing link between the underlying mechanism of disease and validated targets for pharmacological treatment. |
| 492 | 15220194 | Glucose- and interleukin-1beta-induced beta-cell apoptosis requires Ca2+ influx and extracellular signal-regulated kinase (ERK) 1/2 activation and is prevented by a sulfonylurea receptor 1/inwardly rectifying K+ channel 6.2 (SUR/Kir6.2) selective potassium channel opener in human islets. |
| 493 | 15220194 | Therefore, we studied the effect of diazoxide and of the novel potassium channel opener NN414, selective for the beta-cell potassium channel SUR1/Kir6.2, on glucose- and IL-1beta-induced apoptosis and impaired function in human beta-cells. |
| 494 | 15220194 | Exposure of human islets for 4 days to 11.1 and 33.3 mmol/l glucose, 2 ng/ml IL-1beta, or 10 and 100 micromol/l of the sulfonylurea tolbutamide induced beta-cell apoptosis and impaired glucose-stimulated insulin secretion. |
| 495 | 15220194 | By Western blotting with phosphospecific antibodies, glucose and IL-1beta were shown to activate the extracellular signal-regulated kinase (ERK) 1/2, an effect that was abrogated by 3 micromol/l NN414. |
| 496 | 15220194 | Glucose- and interleukin-1beta-induced beta-cell apoptosis requires Ca2+ influx and extracellular signal-regulated kinase (ERK) 1/2 activation and is prevented by a sulfonylurea receptor 1/inwardly rectifying K+ channel 6.2 (SUR/Kir6.2) selective potassium channel opener in human islets. |
| 497 | 15220194 | Therefore, we studied the effect of diazoxide and of the novel potassium channel opener NN414, selective for the beta-cell potassium channel SUR1/Kir6.2, on glucose- and IL-1beta-induced apoptosis and impaired function in human beta-cells. |
| 498 | 15220194 | Exposure of human islets for 4 days to 11.1 and 33.3 mmol/l glucose, 2 ng/ml IL-1beta, or 10 and 100 micromol/l of the sulfonylurea tolbutamide induced beta-cell apoptosis and impaired glucose-stimulated insulin secretion. |
| 499 | 15220194 | By Western blotting with phosphospecific antibodies, glucose and IL-1beta were shown to activate the extracellular signal-regulated kinase (ERK) 1/2, an effect that was abrogated by 3 micromol/l NN414. |
| 500 | 15292032 | Neither of the two protocols affected gene expression of the ion channel-associated proteins Kir6.2, sulfonylurea receptor 1, voltage-dependent calcium channel-alpha1, or Kv2.1. |
| 501 | 15314688 | Foxa2 regulates multiple pathways of insulin secretion. |
| 502 | 15314688 | The regulation of insulin secretion by pancreatic beta cells is perturbed in several diseases, including adult-onset (type 2) diabetes and persistent hyperinsulinemic hypoglycemia of infancy (PHHI). |
| 503 | 15314688 | The first mouse model for PHHI has a conditional deletion of the gene encoding the winged-helix transcription factor Foxa2 (Forkhead box a2, formerly Hepatocyte nuclear factor 3beta) in pancreatic beta cells. |
| 504 | 15314688 | Using isolated islets, we found that Foxa2 deficiency resulted in excessive insulin release in response to amino acids and complete loss of glucose-stimulated insulin secretion. |
| 505 | 15314688 | Most PHHI cases are associated with mutations in SUR1 (Sulfonylurea receptor 1) or KIR6.2 (Inward rectifier K(+) channel member 6.2), which encode the subunits of the ATP-sensitive K(+) channel, and RNA in situ hybridization of mutant mouse islets revealed that expression of both genes is Foxa2 dependent. |
| 506 | 15314688 | Strikingly, one of these genes, Hadhsc, encodes short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase, deficiency of which has been shown to cause PHHI in humans. |
| 507 | 15314688 | Hadhsc is a direct target of Foxa2, as demonstrated by cotransfection as well as in vivo chromatin immunoprecipitation experiments using isolated islets. |
| 508 | 15314688 | Thus, we have established Foxa2 as an essential activator of genes that function in multiple pathways governing insulin secretion. |
| 509 | 15467258 | In studies of various cloned K(ATP) channels, mitiglinide shows a higher selectivity for the beta-cell type of SUR1/Kir6.2 than the cardiac and smooth muscle types of K(ATP) channels in comparison with glibenclamide and glimepiride. |
| 510 | 15533888 | We studied the effects of haloperidol on native ATP-sensitive potassium (K(ATP)) channels in mouse pancreatic beta cells and on cloned Kir6.2/SUR1 channels expressed in HEK293 cells. |
| 511 | 15533888 | Haloperidol blocked cloned Kir6.2/SUR1 and Kir6.2DeltaC36 K(ATP) channels expressed in HEK cells. |
| 512 | 15533888 | We studied the effects of haloperidol on native ATP-sensitive potassium (K(ATP)) channels in mouse pancreatic beta cells and on cloned Kir6.2/SUR1 channels expressed in HEK293 cells. |
| 513 | 15533888 | Haloperidol blocked cloned Kir6.2/SUR1 and Kir6.2DeltaC36 K(ATP) channels expressed in HEK cells. |
| 514 | 15561897 | The adjacent cytoplasmic L0 linker serves a dual function, acting as a tether to link the MDR-like core to the KIR6.2/TMD0 complex and exerting bidirectional control over channel gating via interactions with the NH2-terminus of the KIR. |
| 515 | 15561897 | Elements of the COOH-terminal half of the core recognize a hydrophobic group in glibenclamide, adjacent to the sulfonylurea moiety, to provide selectivity for SUR1, while the benzamido group appears to be in proximity to L0 and the KIR NH2-terminus. |
| 516 | 15561899 | It is comprised of sulfonylurea receptor (SUR)-1 and Kir6.2 proteins. |
| 517 | 15561899 | Binding of Mg nucleotides to the nucleotide-binding domains (NBDs) of SUR1 stimulates channel opening and leads to membrane hyperpolarization and inhibition of insulin secretion. |
| 518 | 15561899 | To elucidate the structural basis of this regulation, we constructed a molecular model of the NBDs of SUR1, based on the crystal structures of mammalian proteins that belong to the same family of ATP-binding cassette transporter proteins. |
| 519 | 15561899 | It is comprised of sulfonylurea receptor (SUR)-1 and Kir6.2 proteins. |
| 520 | 15561899 | Binding of Mg nucleotides to the nucleotide-binding domains (NBDs) of SUR1 stimulates channel opening and leads to membrane hyperpolarization and inhibition of insulin secretion. |
| 521 | 15561899 | To elucidate the structural basis of this regulation, we constructed a molecular model of the NBDs of SUR1, based on the crystal structures of mammalian proteins that belong to the same family of ATP-binding cassette transporter proteins. |
| 522 | 15561899 | It is comprised of sulfonylurea receptor (SUR)-1 and Kir6.2 proteins. |
| 523 | 15561899 | Binding of Mg nucleotides to the nucleotide-binding domains (NBDs) of SUR1 stimulates channel opening and leads to membrane hyperpolarization and inhibition of insulin secretion. |
| 524 | 15561899 | To elucidate the structural basis of this regulation, we constructed a molecular model of the NBDs of SUR1, based on the crystal structures of mammalian proteins that belong to the same family of ATP-binding cassette transporter proteins. |
| 525 | 15561900 | SUR1, the typical pancreatic SUR isoform, shows much higher affinity for glibenclamide but considerably lower affinity for most openers than SUR2. |
| 526 | 15561907 | Formed through association of the Kir6.2 pore and the sulfonylurea receptor, the stress-responsive ATP-sensitive K(+) channels (K(ATP) channels), with their metabolic-sensing capability and broad tissue expression, are potential candidates for integrating the systemic adaptive response to repetitive exercise. |
| 527 | 15561908 | Analysis of Kir6.2 null mice has shown that Kir6.2/SUR1 channels in pancreatic beta-cells and the hypothalamus are essential in glucose-induced insulin secretion and hypoglycemia-induced glucagon secretion, respectively, and that Kir6.2/SUR2 channels are involved in glucose uptake in skeletal muscles. |
| 528 | 15561908 | Our studies of Kir6.2 null and Kir6.1 null mice reveal that KATP channels are critical metabolic sensors in acute metabolic changes, including hyperglycemia, hypoglycemia, ischemia, and hypoxia. |
| 529 | 15561922 | In the present study, we examined the effects of cAMP and ATP on the interaction of cAMP-GEFII and sulfonylurea receptor-1 (SUR1). |
| 530 | 15561922 | In addition, SUR1, cAMP-GEFII, and Piccolo could form a complex. |
| 531 | 15561922 | In the present study, we examined the effects of cAMP and ATP on the interaction of cAMP-GEFII and sulfonylurea receptor-1 (SUR1). |
| 532 | 15561922 | In addition, SUR1, cAMP-GEFII, and Piccolo could form a complex. |
| 533 | 15562009 | Congenital hyperinsulinism (HI) is most commonly caused by recessive mutations of the pancreatic beta-cell ATP-sensitive potassium channel (K(ATP)), encoded by two genes on chromosome 11p, SUR1 and Kir6.2. |
| 534 | 15562009 | The two mutations that have been best studied, SUR1 g3992-9a and SUR1 delF1388, are null mutations yielding nonfunctional channels and are characterized by nonresponsiveness to diazoxide, a channel agonist, and absence of acute insulin responses (AIRs) to tolbutamide, a channel antagonist, or leucine. |
| 535 | 15562009 | To examine phenotypes of other K(ATP) mutations, we measured AIRs to calcium, leucine, glucose, and tolbutamide in infants with recessive SUR1 or Kir6.2 mutations expressed as diffuse HI (n = 8) or focal HI (n = 14). |
| 536 | 15562009 | Congenital hyperinsulinism (HI) is most commonly caused by recessive mutations of the pancreatic beta-cell ATP-sensitive potassium channel (K(ATP)), encoded by two genes on chromosome 11p, SUR1 and Kir6.2. |
| 537 | 15562009 | The two mutations that have been best studied, SUR1 g3992-9a and SUR1 delF1388, are null mutations yielding nonfunctional channels and are characterized by nonresponsiveness to diazoxide, a channel agonist, and absence of acute insulin responses (AIRs) to tolbutamide, a channel antagonist, or leucine. |
| 538 | 15562009 | To examine phenotypes of other K(ATP) mutations, we measured AIRs to calcium, leucine, glucose, and tolbutamide in infants with recessive SUR1 or Kir6.2 mutations expressed as diffuse HI (n = 8) or focal HI (n = 14). |
| 539 | 15562009 | Congenital hyperinsulinism (HI) is most commonly caused by recessive mutations of the pancreatic beta-cell ATP-sensitive potassium channel (K(ATP)), encoded by two genes on chromosome 11p, SUR1 and Kir6.2. |
| 540 | 15562009 | The two mutations that have been best studied, SUR1 g3992-9a and SUR1 delF1388, are null mutations yielding nonfunctional channels and are characterized by nonresponsiveness to diazoxide, a channel agonist, and absence of acute insulin responses (AIRs) to tolbutamide, a channel antagonist, or leucine. |
| 541 | 15562009 | To examine phenotypes of other K(ATP) mutations, we measured AIRs to calcium, leucine, glucose, and tolbutamide in infants with recessive SUR1 or Kir6.2 mutations expressed as diffuse HI (n = 8) or focal HI (n = 14). |
| 542 | 15563985 | K(ATP) channels are composed of pore-forming inwardly rectifying potassium channel (Kir6.2 or Kir6.1) subunits and sulfonylurea receptor (SUR1, SUR2A, or SUR2B) subunits. |
| 543 | 15563985 | Kir6.2 or Kir6.1 subunits conjoined with a SUR subunit constitute the various tissue-specific K(ATP) channels with distinct pharmacological properties. |
| 544 | 15563985 | K(ATP) channels are composed of pore-forming inwardly rectifying potassium channel (Kir6.2 or Kir6.1) subunits and sulfonylurea receptor (SUR1, SUR2A, or SUR2B) subunits. |
| 545 | 15563985 | Kir6.2 or Kir6.1 subunits conjoined with a SUR subunit constitute the various tissue-specific K(ATP) channels with distinct pharmacological properties. |
| 546 | 15579791 | Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes. |
| 547 | 15579791 | We investigated whether common polymorphisms in the SUR1 and Kir6.2 genes are associated with increased risk of type 2 diabetes in 490 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study. |
| 548 | 15579791 | Subjects with both the high-risk haplotype of the SUR1 gene and the 23K allele of the Kir6.2 gene had a 6-fold risk for the conversion to diabetes compared with those without any of these risk genotypes (OR, 5.68; 95% CI, 1.75-18.32; P = 0.004). |
| 549 | 15579791 | We conclude that the polymorphisms of the SUR1 gene predicted the conversion from impaired glucose tolerance to type 2 diabetes and that the effect of these polymorphisms on diabetes risk was additive with the E23K polymorphism of the Kir6.2 gene. |
| 550 | 15579791 | Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes. |
| 551 | 15579791 | We investigated whether common polymorphisms in the SUR1 and Kir6.2 genes are associated with increased risk of type 2 diabetes in 490 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study. |
| 552 | 15579791 | Subjects with both the high-risk haplotype of the SUR1 gene and the 23K allele of the Kir6.2 gene had a 6-fold risk for the conversion to diabetes compared with those without any of these risk genotypes (OR, 5.68; 95% CI, 1.75-18.32; P = 0.004). |
| 553 | 15579791 | We conclude that the polymorphisms of the SUR1 gene predicted the conversion from impaired glucose tolerance to type 2 diabetes and that the effect of these polymorphisms on diabetes risk was additive with the E23K polymorphism of the Kir6.2 gene. |
| 554 | 15579791 | Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes. |
| 555 | 15579791 | We investigated whether common polymorphisms in the SUR1 and Kir6.2 genes are associated with increased risk of type 2 diabetes in 490 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study. |
| 556 | 15579791 | Subjects with both the high-risk haplotype of the SUR1 gene and the 23K allele of the Kir6.2 gene had a 6-fold risk for the conversion to diabetes compared with those without any of these risk genotypes (OR, 5.68; 95% CI, 1.75-18.32; P = 0.004). |
| 557 | 15579791 | We conclude that the polymorphisms of the SUR1 gene predicted the conversion from impaired glucose tolerance to type 2 diabetes and that the effect of these polymorphisms on diabetes risk was additive with the E23K polymorphism of the Kir6.2 gene. |
| 558 | 15579791 | Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes. |
| 559 | 15579791 | We investigated whether common polymorphisms in the SUR1 and Kir6.2 genes are associated with increased risk of type 2 diabetes in 490 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study. |
| 560 | 15579791 | Subjects with both the high-risk haplotype of the SUR1 gene and the 23K allele of the Kir6.2 gene had a 6-fold risk for the conversion to diabetes compared with those without any of these risk genotypes (OR, 5.68; 95% CI, 1.75-18.32; P = 0.004). |
| 561 | 15579791 | We conclude that the polymorphisms of the SUR1 gene predicted the conversion from impaired glucose tolerance to type 2 diabetes and that the effect of these polymorphisms on diabetes risk was additive with the E23K polymorphism of the Kir6.2 gene. |
| 562 | 15583126 | To determine the molecular basis of these different phenotypes, we expressed wild-type or mutant (R201C, Q52R, or V59G) Kir6.2/sulfonylurea receptor 1 channels in Xenopus oocytes. |
| 563 | 15630453 | The abundance of mRNAs for Glut2 and HNF3beta was reduced in islets of betaPKClambda(-/-) mice, and the expression of genes regulated by HNF3beta was also affected (that of Sur1 and Kir6.2 genes was reduced, whereas that of hexokinase 1 and hexokinase 2 genes was increased). |
| 564 | 15630453 | Normalization of HNF3beta expression by infection of islets from betaPKClambda(-/-) mice with an adenoviral vector significantly reversed the defect in glucose-stimulated insulin secretion. |
| 565 | 15631623 | The three Fox (forkhead box) group A genes, Foxa1, Foxa2 and Foxa3, are expressed in embryonic endoderm, the germ layer that gives rise to the digestive system, and contribute to the specification of the pancreas and the regulation of glucose homoeostasis. |
| 566 | 15631623 | Deletion of the Foxa2 gene in pancreatic beta-cells in mice results in a phenotype resembling PHHI (persistent hyperinsulinaemic hypoglycaemia of infancy). |
| 567 | 15631623 | Molecular analyses have demonstrated that Foxa2 is an important regulator of the genes encoding Sur1, Kir6.2 and Schad (short chain L-3-hydroxyacyl-CoA dehydrogenase), mutation of which causes PHHI in humans. |
| 568 | 15631623 | An additional winged-helix protein, Foxo1, contributes to pancreatic beta-cell function by regulating the Pdx1 gene, which is required for pancreatic development in cooperation with Foxa2. |
| 569 | 15652236 | Role of two adjacent cytoplasmic tyrosine residues in MRP1 (ABCC1) transport activity and sensitivity to sulfonylureas. |
| 570 | 15652236 | The human ATP-binding cassette (ABC) protein MRP1 causes resistance to many anticancer drugs and is also a primary active transporter of conjugated metabolites and endogenous organic anions, including leukotriene C(4) (LTC(4)) and glutathione (GSH). |
| 571 | 15652236 | The sulfonylurea receptors SUR1 and SUR2 are related ABC proteins with the same domain structure as MRP1, but serve as regulators of the K(+) channel Kir6.2. |
| 572 | 15652236 | Despite their functional differences, the activity of both SUR1/2 and MRP1 can be blocked by glibenclamide, a sulfonylurea used to treat diabetes. |
| 573 | 15652236 | We have now investigated the effect of mutating Tyr(1189) and Tyr(1190) in the comparable region of MRP1 on its transport activity and sulfonylurea sensitivity. |
| 574 | 15652236 | Ala and Ser substitutions of Tyr(1189) and Tyr(1190) caused a > or =50% decrease in the ability of MRP1 to transport different organic anions, and a decrease in LTC(4) photolabeling. |
| 575 | 15652236 | We conclude that MRP1 Tyr(1189) and Tyr(1190), unlike the corresponding residues in SUR1, are not involved in its differential sensitivity to sulfonylureas, but nevertheless, may be involved in the transport activity of MRP1, especially with respect to GSH. |
| 576 | 15652236 | Role of two adjacent cytoplasmic tyrosine residues in MRP1 (ABCC1) transport activity and sensitivity to sulfonylureas. |
| 577 | 15652236 | The human ATP-binding cassette (ABC) protein MRP1 causes resistance to many anticancer drugs and is also a primary active transporter of conjugated metabolites and endogenous organic anions, including leukotriene C(4) (LTC(4)) and glutathione (GSH). |
| 578 | 15652236 | The sulfonylurea receptors SUR1 and SUR2 are related ABC proteins with the same domain structure as MRP1, but serve as regulators of the K(+) channel Kir6.2. |
| 579 | 15652236 | Despite their functional differences, the activity of both SUR1/2 and MRP1 can be blocked by glibenclamide, a sulfonylurea used to treat diabetes. |
| 580 | 15652236 | We have now investigated the effect of mutating Tyr(1189) and Tyr(1190) in the comparable region of MRP1 on its transport activity and sulfonylurea sensitivity. |
| 581 | 15652236 | Ala and Ser substitutions of Tyr(1189) and Tyr(1190) caused a > or =50% decrease in the ability of MRP1 to transport different organic anions, and a decrease in LTC(4) photolabeling. |
| 582 | 15652236 | We conclude that MRP1 Tyr(1189) and Tyr(1190), unlike the corresponding residues in SUR1, are not involved in its differential sensitivity to sulfonylureas, but nevertheless, may be involved in the transport activity of MRP1, especially with respect to GSH. |
| 583 | 15652236 | Role of two adjacent cytoplasmic tyrosine residues in MRP1 (ABCC1) transport activity and sensitivity to sulfonylureas. |
| 584 | 15652236 | The human ATP-binding cassette (ABC) protein MRP1 causes resistance to many anticancer drugs and is also a primary active transporter of conjugated metabolites and endogenous organic anions, including leukotriene C(4) (LTC(4)) and glutathione (GSH). |
| 585 | 15652236 | The sulfonylurea receptors SUR1 and SUR2 are related ABC proteins with the same domain structure as MRP1, but serve as regulators of the K(+) channel Kir6.2. |
| 586 | 15652236 | Despite their functional differences, the activity of both SUR1/2 and MRP1 can be blocked by glibenclamide, a sulfonylurea used to treat diabetes. |
| 587 | 15652236 | We have now investigated the effect of mutating Tyr(1189) and Tyr(1190) in the comparable region of MRP1 on its transport activity and sulfonylurea sensitivity. |
| 588 | 15652236 | Ala and Ser substitutions of Tyr(1189) and Tyr(1190) caused a > or =50% decrease in the ability of MRP1 to transport different organic anions, and a decrease in LTC(4) photolabeling. |
| 589 | 15652236 | We conclude that MRP1 Tyr(1189) and Tyr(1190), unlike the corresponding residues in SUR1, are not involved in its differential sensitivity to sulfonylureas, but nevertheless, may be involved in the transport activity of MRP1, especially with respect to GSH. |
| 590 | 15678092 | We further explore how the binding properties of repaglinide and glibenclamide are affected by functional uncoupling of SUR1 and Kir6.2 in Kir6.2DeltaN14/SUR1 channels. |
| 591 | 15678092 | Glibenclamide, tolbutamide and nateglinide all bound with marginally lower affinity to SUR1 than to Kir6.2/SUR1. 3. |
| 592 | 15678092 | The results suggest that Kir6.2 causes a conformational change in SUR1 required for high-affinity repaglinide binding, or that the high-affinity repaglinide-binding site includes contributions from both SUR1 and Kir6.2. |
| 593 | 15678092 | We further explore how the binding properties of repaglinide and glibenclamide are affected by functional uncoupling of SUR1 and Kir6.2 in Kir6.2DeltaN14/SUR1 channels. |
| 594 | 15678092 | Glibenclamide, tolbutamide and nateglinide all bound with marginally lower affinity to SUR1 than to Kir6.2/SUR1. 3. |
| 595 | 15678092 | The results suggest that Kir6.2 causes a conformational change in SUR1 required for high-affinity repaglinide binding, or that the high-affinity repaglinide-binding site includes contributions from both SUR1 and Kir6.2. |
| 596 | 15678092 | We further explore how the binding properties of repaglinide and glibenclamide are affected by functional uncoupling of SUR1 and Kir6.2 in Kir6.2DeltaN14/SUR1 channels. |
| 597 | 15678092 | Glibenclamide, tolbutamide and nateglinide all bound with marginally lower affinity to SUR1 than to Kir6.2/SUR1. 3. |
| 598 | 15678092 | The results suggest that Kir6.2 causes a conformational change in SUR1 required for high-affinity repaglinide binding, or that the high-affinity repaglinide-binding site includes contributions from both SUR1 and Kir6.2. |
| 599 | 15718250 | Functional characterization of the TNDM associated mutations was performed by expressing the mutated Kir6.2 with SUR1 in Xenopus laevis oocytes. |
| 600 | 15842514 | Common variants in the ATP-sensitive K+ channel genes KCNJ11 (Kir6.2) and ABCC8 (SUR1) in relation to glucose intolerance: population-based studies and meta-analyses. |
| 601 | 15864298 | We investigated the functional effects of the I296L mutation by expressing wild-type or mutant Kir6.2/SUR1 channels in Xenopus oocytes. |
| 602 | 15893323 | K(ATP) channels generated from coexpression of Kir6.2 with SUR1 exhibit greater MgADP stimulation than channels generated from coexpression of Kir6.2 with SUR2A. |
| 603 | 15962003 | ATP-sensitive K(+) (K(ATP)) channels, comprised of pore-forming Kir6.2 and regulatory SUR1 subunits, play a critical role in regulating insulin secretion. |
| 604 | 15962003 | Binding of ATP to Kir6.2 inhibits, whereas interaction of MgATP with SUR1 activates, K(ATP) channels. |
| 605 | 15962003 | Both mutations also altered Kir6.2/SUR1 interactions, enhancing the stimulatory effect of MgATP (which is mediated via SUR1). |
| 606 | 15962003 | ATP-sensitive K(+) (K(ATP)) channels, comprised of pore-forming Kir6.2 and regulatory SUR1 subunits, play a critical role in regulating insulin secretion. |
| 607 | 15962003 | Binding of ATP to Kir6.2 inhibits, whereas interaction of MgATP with SUR1 activates, K(ATP) channels. |
| 608 | 15962003 | Both mutations also altered Kir6.2/SUR1 interactions, enhancing the stimulatory effect of MgATP (which is mediated via SUR1). |
| 609 | 15962003 | ATP-sensitive K(+) (K(ATP)) channels, comprised of pore-forming Kir6.2 and regulatory SUR1 subunits, play a critical role in regulating insulin secretion. |
| 610 | 15962003 | Binding of ATP to Kir6.2 inhibits, whereas interaction of MgATP with SUR1 activates, K(ATP) channels. |
| 611 | 15962003 | Both mutations also altered Kir6.2/SUR1 interactions, enhancing the stimulatory effect of MgATP (which is mediated via SUR1). |
| 612 | 15963039 | K(ATP) channels are hetero-octameric complexes comprising two subunits Kir6.2 and sulfonylurea receptor 1 (SUR1). |
| 613 | 15963039 | On the other hand, now there is evidence of an association between polymorphisms in the Kir6.2 gene and type 2 diabetes mellitus, mutations in the Kir6.2 gene and neonatal diabetes mellitus, and mutations in the SUR1 gene and diabetes mellitus. |
| 614 | 15963039 | K(ATP) channels are hetero-octameric complexes comprising two subunits Kir6.2 and sulfonylurea receptor 1 (SUR1). |
| 615 | 15963039 | On the other hand, now there is evidence of an association between polymorphisms in the Kir6.2 gene and type 2 diabetes mellitus, mutations in the Kir6.2 gene and neonatal diabetes mellitus, and mutations in the SUR1 gene and diabetes mellitus. |
| 616 | 16186397 | Proposed mechanisms include the activation of the autonomic nervous system via glucose-sensing neurons in the central nervous system, via the regulation of glucagon secretion by intra-islet insulin and zinc concentrations, or via direct ionic control, all mechanisms that involve high-affinity sulfonylurea receptor/inwardly rectifying potassium channel-type ATP-sensitive K(+) channels. |
| 617 | 16198094 | The 2 subunits of the K(+)(ATP) channel are encoded by either the sulfonylurea receptor gene (SUR1 or ABCC8) or the inward-rectifying potassium channel gene (KIR6.2. or KCNJ11), both located in the 11p15.1 region. |
| 618 | 16198094 | Focal CHI has been shown to result from a paternally inherited mutation on the SUR1 or KIR6.2 gene and loss of the maternal 11p15 allele restricted to the pancreatic lesion. |
| 619 | 16198094 | Diffuse HI, frequently due to mutations of the SUR1 or KIR6.2 genes of autosomal recessive inheritance is genetically heterogeneous. |
| 620 | 16198094 | The 2 subunits of the K(+)(ATP) channel are encoded by either the sulfonylurea receptor gene (SUR1 or ABCC8) or the inward-rectifying potassium channel gene (KIR6.2. or KCNJ11), both located in the 11p15.1 region. |
| 621 | 16198094 | Focal CHI has been shown to result from a paternally inherited mutation on the SUR1 or KIR6.2 gene and loss of the maternal 11p15 allele restricted to the pancreatic lesion. |
| 622 | 16198094 | Diffuse HI, frequently due to mutations of the SUR1 or KIR6.2 genes of autosomal recessive inheritance is genetically heterogeneous. |
| 623 | 16198094 | The 2 subunits of the K(+)(ATP) channel are encoded by either the sulfonylurea receptor gene (SUR1 or ABCC8) or the inward-rectifying potassium channel gene (KIR6.2. or KCNJ11), both located in the 11p15.1 region. |
| 624 | 16198094 | Focal CHI has been shown to result from a paternally inherited mutation on the SUR1 or KIR6.2 gene and loss of the maternal 11p15 allele restricted to the pancreatic lesion. |
| 625 | 16198094 | Diffuse HI, frequently due to mutations of the SUR1 or KIR6.2 genes of autosomal recessive inheritance is genetically heterogeneous. |
| 626 | 16306272 | Sulfonylurea receptor 1 (SUR1) is the regulatory subunit of the pancreatic ATP-sensitive K+ channel (K(ATP) channel), which is essential for triggering insulin secretion via membrane depolarization. |
| 627 | 16306272 | To investigate the role of SUR in apoptosis induction, we tested the effect of glibenclamide on recombinant human embryonic kidney 293 cells expressing either SUR1, the smooth muscular isoform SUR2B, or the mutant SUR1(M1289T) at which a single amino acid in transmembrane helix 17 (TM17) was exchanged by the corresponding amino acid of SUR2. |
| 628 | 16306272 | By analyzing cell detachment, nuclear condensation, DNA fragmentation, and caspase-3-like activity, we observed a SUR1-specific enhancement of glibenclamide-induced apoptosis that was not seen in SUR2B, SUR1(M1289T), or control cells. |
| 629 | 16306272 | This effect does not require the presence of functional Kir6.2-containing K(ATP) channels, which points to additional, so far unknown functions of SUR. |
| 630 | 16306272 | Sulfonylurea receptor 1 (SUR1) is the regulatory subunit of the pancreatic ATP-sensitive K+ channel (K(ATP) channel), which is essential for triggering insulin secretion via membrane depolarization. |
| 631 | 16306272 | To investigate the role of SUR in apoptosis induction, we tested the effect of glibenclamide on recombinant human embryonic kidney 293 cells expressing either SUR1, the smooth muscular isoform SUR2B, or the mutant SUR1(M1289T) at which a single amino acid in transmembrane helix 17 (TM17) was exchanged by the corresponding amino acid of SUR2. |
| 632 | 16306272 | By analyzing cell detachment, nuclear condensation, DNA fragmentation, and caspase-3-like activity, we observed a SUR1-specific enhancement of glibenclamide-induced apoptosis that was not seen in SUR2B, SUR1(M1289T), or control cells. |
| 633 | 16306272 | This effect does not require the presence of functional Kir6.2-containing K(ATP) channels, which points to additional, so far unknown functions of SUR. |
| 634 | 16306272 | Sulfonylurea receptor 1 (SUR1) is the regulatory subunit of the pancreatic ATP-sensitive K+ channel (K(ATP) channel), which is essential for triggering insulin secretion via membrane depolarization. |
| 635 | 16306272 | To investigate the role of SUR in apoptosis induction, we tested the effect of glibenclamide on recombinant human embryonic kidney 293 cells expressing either SUR1, the smooth muscular isoform SUR2B, or the mutant SUR1(M1289T) at which a single amino acid in transmembrane helix 17 (TM17) was exchanged by the corresponding amino acid of SUR2. |
| 636 | 16306272 | By analyzing cell detachment, nuclear condensation, DNA fragmentation, and caspase-3-like activity, we observed a SUR1-specific enhancement of glibenclamide-induced apoptosis that was not seen in SUR2B, SUR1(M1289T), or control cells. |
| 637 | 16306272 | This effect does not require the presence of functional Kir6.2-containing K(ATP) channels, which points to additional, so far unknown functions of SUR. |
| 638 | 16306272 | Sulfonylurea receptor 1 (SUR1) is the regulatory subunit of the pancreatic ATP-sensitive K+ channel (K(ATP) channel), which is essential for triggering insulin secretion via membrane depolarization. |
| 639 | 16306272 | To investigate the role of SUR in apoptosis induction, we tested the effect of glibenclamide on recombinant human embryonic kidney 293 cells expressing either SUR1, the smooth muscular isoform SUR2B, or the mutant SUR1(M1289T) at which a single amino acid in transmembrane helix 17 (TM17) was exchanged by the corresponding amino acid of SUR2. |
| 640 | 16306272 | By analyzing cell detachment, nuclear condensation, DNA fragmentation, and caspase-3-like activity, we observed a SUR1-specific enhancement of glibenclamide-induced apoptosis that was not seen in SUR2B, SUR1(M1289T), or control cells. |
| 641 | 16306272 | This effect does not require the presence of functional Kir6.2-containing K(ATP) channels, which points to additional, so far unknown functions of SUR. |
| 642 | 16332676 | Loss of KATP channel function due to mutations in ABCC8 or KCNJ11, genes that encode the sulfonylurea receptor 1 or the inward rectifier Kir6.2 subunit of the channel, is a major cause of congenital hyperinsulinism. |
| 643 | 16339180 | The greater ATP inhibition of mutant Kir6.2/SUR2A than of Kir6.2/SUR1 can explain why gain-of-function Kir6.2 mutations manifest effects in brain and beta-cells but not in the heart. |
| 644 | 16339272 | Overexpression of Kruppel-like factor 7 regulates adipocytokine gene expressions in human adipocytes and inhibits glucose-induced insulin secretion in pancreatic beta-cell line. |
| 645 | 16339272 | We have identified Kruppel-like factor 7 (KLF7) as a new candidate for conferring susceptibility to type 2 diabetes. |
| 646 | 16339272 | In human adipocytes overexpressing KLF7, the expression of adiponectin and leptin was decreased compared with that in control cells, whereas expression of IL-6 was increased. |
| 647 | 16339272 | In the insulin-secreting cell line (HIT-T15 cells), the expression and glucose-induced secretion of insulin were significantly suppressed in KLF7-overexpressed cells compared with control cells, accompanied by the reduction in the expression of glucose transporter 2, sulfonylurea receptor 1, Kir6.2, and pancreatic-duodenal homeobox factor 1. |
| 648 | 16339272 | We also found that the overexpression of KLF7 resulted in the decrease of hexokinase 2 expression in smooth muscle cells, and of glucose transporter 2 expression in the HepG2 cells. |
| 649 | 16339272 | These results suggest that KLF7 may contribute to the pathogenesis of type 2 diabetes through an impairment of insulin biosynthesis and secretion in pancreatic beta-cells and a reduction of insulin sensitivity in peripheral tissues. |
| 650 | 16377800 | Mutations in the hepatocyte nuclear factor (HNF)-4alpha gene cause a form of maturity-onset diabetes of the young (MODY1) that is characterized by impairment of glucose-stimulated insulin secretion by pancreatic beta-cells. |
| 651 | 16377800 | The betaHNF-4alphaKO mice exhibited impairment of glucose-stimulated insulin secretion, which is a characteristic of MODY1. |
| 652 | 16377800 | Pancreatic islet morphology, beta-cell mass, and insulin content were normal in the HNF-4alpha mutant mice. |
| 653 | 16377800 | Expression levels of Kir6.2 and SUR1 proteins in the betaHNF-4alphaKO mice were unchanged as compared with control mice. |
| 654 | 16380471 | The focal condition is caused by a paternally inherited mutation in one of the genes encoding the subunits of the beta-cell ATP-sensitive potassium channel (SUR1/ABCC8 or Kir6.2/KCNJ11) and somatic loss of maternal 11p15 alleles within the affected area. |
| 655 | 16416420 | Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism. |
| 656 | 16416420 | The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1. |
| 657 | 16416420 | It has been known for some time that loss of function mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1, can cause oversecretion of insulin and result in hyperinsulinemia (HI) of infancy; however, heterozygous activating mutations in KCNJ11 that result in the opposite phenotype of diabetes have recently been described. |
| 658 | 16416420 | Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism. |
| 659 | 16416420 | The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1. |
| 660 | 16416420 | It has been known for some time that loss of function mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1, can cause oversecretion of insulin and result in hyperinsulinemia (HI) of infancy; however, heterozygous activating mutations in KCNJ11 that result in the opposite phenotype of diabetes have recently been described. |
| 661 | 16416420 | Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism. |
| 662 | 16416420 | The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1. |
| 663 | 16416420 | It has been known for some time that loss of function mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1, can cause oversecretion of insulin and result in hyperinsulinemia (HI) of infancy; however, heterozygous activating mutations in KCNJ11 that result in the opposite phenotype of diabetes have recently been described. |
| 664 | 16475928 | Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives. |
| 665 | 16475928 | In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin. |
| 666 | 16475928 | The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues. |
| 667 | 16475928 | Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes. |
| 668 | 16475928 | Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI). |
| 669 | 16475928 | Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS. |
| 670 | 16475928 | The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued. |
| 671 | 16475928 | NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies. |
| 672 | 16475928 | Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives. |
| 673 | 16475928 | In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin. |
| 674 | 16475928 | The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues. |
| 675 | 16475928 | Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes. |
| 676 | 16475928 | Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI). |
| 677 | 16475928 | Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS. |
| 678 | 16475928 | The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued. |
| 679 | 16475928 | NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies. |
| 680 | 16475928 | Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives. |
| 681 | 16475928 | In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin. |
| 682 | 16475928 | The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues. |
| 683 | 16475928 | Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes. |
| 684 | 16475928 | Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI). |
| 685 | 16475928 | Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS. |
| 686 | 16475928 | The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued. |
| 687 | 16475928 | NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies. |
| 688 | 16475928 | Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives. |
| 689 | 16475928 | In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin. |
| 690 | 16475928 | The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues. |
| 691 | 16475928 | Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes. |
| 692 | 16475928 | Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI). |
| 693 | 16475928 | Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS. |
| 694 | 16475928 | The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued. |
| 695 | 16475928 | NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies. |
| 696 | 16475928 | Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives. |
| 697 | 16475928 | In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin. |
| 698 | 16475928 | The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues. |
| 699 | 16475928 | Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes. |
| 700 | 16475928 | Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI). |
| 701 | 16475928 | Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS. |
| 702 | 16475928 | The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued. |
| 703 | 16475928 | NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies. |
| 704 | 16475928 | Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives. |
| 705 | 16475928 | In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin. |
| 706 | 16475928 | The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues. |
| 707 | 16475928 | Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes. |
| 708 | 16475928 | Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI). |
| 709 | 16475928 | Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS. |
| 710 | 16475928 | The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued. |
| 711 | 16475928 | NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies. |
| 712 | 16475928 | Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives. |
| 713 | 16475928 | In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin. |
| 714 | 16475928 | The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues. |
| 715 | 16475928 | Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes. |
| 716 | 16475928 | Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI). |
| 717 | 16475928 | Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS. |
| 718 | 16475928 | The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued. |
| 719 | 16475928 | NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies. |
| 720 | 16475928 | Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives. |
| 721 | 16475928 | In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin. |
| 722 | 16475928 | The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues. |
| 723 | 16475928 | Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes. |
| 724 | 16475928 | Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI). |
| 725 | 16475928 | Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS. |
| 726 | 16475928 | The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued. |
| 727 | 16475928 | NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies. |
| 728 | 16613899 | Residue F132 shows evolutionary conservation across species and is located in the first set of transmembrane helices (TMD0) of SUR1, which is proposed to interact with Kir6.2. |
| 729 | 16613899 | The functional consequence of this ABCC8 mutation mirrors that of KCNJ11 mutations causing neonatal diabetes and provides new insights into the interaction of Kir6.2 and SUR1. |
| 730 | 16613899 | Residue F132 shows evolutionary conservation across species and is located in the first set of transmembrane helices (TMD0) of SUR1, which is proposed to interact with Kir6.2. |
| 731 | 16613899 | The functional consequence of this ABCC8 mutation mirrors that of KCNJ11 mutations causing neonatal diabetes and provides new insights into the interaction of Kir6.2 and SUR1. |
| 732 | 16731833 | Wild-type or mutant Kir6.2/SUR1 channels were examined by heterologous expression in Xenopus oocytes. |
| 733 | 16807374 | Microarray analysis of blood microvessels from PDGF-B and PDGF-Rbeta mutant mice identifies novel markers for brain pericytes. |
| 734 | 16807374 | Here we describe an approach to identify pericyte markers based on transcription profiling of pericyte-deficient brain microvessels isolated from platelet-derived growth factor (PDGF-B)-/- and PDGF beta receptor (PDGFRbeta)-/- mouse mutants. |
| 735 | 16807374 | Of candidates for novel pericyte markers, we selected ATP-sensitive potassium-channel Kir6.1 (also known as Kcnj8) and sulfonylurea receptor 2, (SUR2, also known as Abcc9), both part of the same channel complex, as well as delta homologue 1 (DLK1) for in situ hybridization, which demonstrated their specific expression in brain pericytes of mouse embryos. |
| 736 | 16821773 | Compound 1a (NN414) is a potent opener of Kir6.2/SUR1 K(ATP) channels. |
| 737 | 16821773 | Several compounds, e.g., 6-chloro-3-(1-methyl-1-phenylethyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (1h), were found to be potent openers of Kir6.2/SUR1 K(ATP) channels and were able to suppress glucose-stimulated insulin release from rat islets in vitro (EC(50) = 0.04 +/- 0.01 muM) and in vivo after intravenous or peroral administration to hyperinsulinemic obese Zucker rats (ED(50) = 4.0 mg/kg). |
| 738 | 16821773 | Compound 1a (NN414) is a potent opener of Kir6.2/SUR1 K(ATP) channels. |
| 739 | 16821773 | Several compounds, e.g., 6-chloro-3-(1-methyl-1-phenylethyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (1h), were found to be potent openers of Kir6.2/SUR1 K(ATP) channels and were able to suppress glucose-stimulated insulin release from rat islets in vitro (EC(50) = 0.04 +/- 0.01 muM) and in vivo after intravenous or peroral administration to hyperinsulinemic obese Zucker rats (ED(50) = 4.0 mg/kg). |
| 740 | 16873704 | We examined the association of variants in genes encoding several transcription factors (TCF1, TCF2, HNF4A, ISL1, IPF1, NEUROG3, PAX6, NKX2-2, NKX6-1, and NEUROD1) and genes encoding the ATP-sensitive K(+) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) with type 2 diabetes in a Japanese cohort of 2,834 subjects. |
| 741 | 16897043 | ABCC8 and ABCC9: ABC transporters that regulate K+ channels. |
| 742 | 16897043 | The sulfonylurea receptors (SURs) ABCC8/SUR1 and ABCC9/SUR2 are members of the C-branch of the transport adenosine triphosphatase superfamily. |
| 743 | 16897043 | Unlike their brethren, the SURs have no identified transport function; instead, evolution has matched these molecules with K(+) selective pores, either K(IR)6.1/KCNJ8 or K(IR)6.2/KCNJ11, to assemble adenosine triphosphate (ATP)-sensitive K(+) channels found in endocrine cells, neurons, and both smooth and striated muscle. |
| 744 | 16897043 | Mutations in either subunit can alter this balance and, in the case of the SUR1/KIR6.2 channels found in neurons and insulin-secreting pancreatic beta cells, are the cause of monogenic forms of hyperinsulinemic hypoglycemia and neonatal diabetes. |
| 745 | 16897043 | ABCC8 and ABCC9: ABC transporters that regulate K+ channels. |
| 746 | 16897043 | The sulfonylurea receptors (SURs) ABCC8/SUR1 and ABCC9/SUR2 are members of the C-branch of the transport adenosine triphosphatase superfamily. |
| 747 | 16897043 | Unlike their brethren, the SURs have no identified transport function; instead, evolution has matched these molecules with K(+) selective pores, either K(IR)6.1/KCNJ8 or K(IR)6.2/KCNJ11, to assemble adenosine triphosphate (ATP)-sensitive K(+) channels found in endocrine cells, neurons, and both smooth and striated muscle. |
| 748 | 16897043 | Mutations in either subunit can alter this balance and, in the case of the SUR1/KIR6.2 channels found in neurons and insulin-secreting pancreatic beta cells, are the cause of monogenic forms of hyperinsulinemic hypoglycemia and neonatal diabetes. |
| 749 | 16897043 | ABCC8 and ABCC9: ABC transporters that regulate K+ channels. |
| 750 | 16897043 | The sulfonylurea receptors (SURs) ABCC8/SUR1 and ABCC9/SUR2 are members of the C-branch of the transport adenosine triphosphatase superfamily. |
| 751 | 16897043 | Unlike their brethren, the SURs have no identified transport function; instead, evolution has matched these molecules with K(+) selective pores, either K(IR)6.1/KCNJ8 or K(IR)6.2/KCNJ11, to assemble adenosine triphosphate (ATP)-sensitive K(+) channels found in endocrine cells, neurons, and both smooth and striated muscle. |
| 752 | 16897043 | Mutations in either subunit can alter this balance and, in the case of the SUR1/KIR6.2 channels found in neurons and insulin-secreting pancreatic beta cells, are the cause of monogenic forms of hyperinsulinemic hypoglycemia and neonatal diabetes. |
| 753 | 16897043 | ABCC8 and ABCC9: ABC transporters that regulate K+ channels. |
| 754 | 16897043 | The sulfonylurea receptors (SURs) ABCC8/SUR1 and ABCC9/SUR2 are members of the C-branch of the transport adenosine triphosphatase superfamily. |
| 755 | 16897043 | Unlike their brethren, the SURs have no identified transport function; instead, evolution has matched these molecules with K(+) selective pores, either K(IR)6.1/KCNJ8 or K(IR)6.2/KCNJ11, to assemble adenosine triphosphate (ATP)-sensitive K(+) channels found in endocrine cells, neurons, and both smooth and striated muscle. |
| 756 | 16897043 | Mutations in either subunit can alter this balance and, in the case of the SUR1/KIR6.2 channels found in neurons and insulin-secreting pancreatic beta cells, are the cause of monogenic forms of hyperinsulinemic hypoglycemia and neonatal diabetes. |
| 757 | 16956886 | Reduced K(ATP) channel expression caused by mutations in the channel proteins: sulfonylurea receptor 1 (SUR1) and Kir6.2, results in loss of channel function as seen in congenital hyperinsulinism. |
| 758 | 16956886 | Interestingly, rescue of the trafficking defects requires mutant SUR1 to be co-expressed with Kir6.2, suggesting that the channel complex, rather than SUR1 alone, is the drug target. |
| 759 | 16956886 | Observations that sulfonylureas also reverse trafficking defects caused by neonatal diabetes-associated Kir6.2 mutations in a way that is dependent on intact sulfonylurea binding sites in SUR1 further support this notion. |
| 760 | 16956886 | Reduced K(ATP) channel expression caused by mutations in the channel proteins: sulfonylurea receptor 1 (SUR1) and Kir6.2, results in loss of channel function as seen in congenital hyperinsulinism. |
| 761 | 16956886 | Interestingly, rescue of the trafficking defects requires mutant SUR1 to be co-expressed with Kir6.2, suggesting that the channel complex, rather than SUR1 alone, is the drug target. |
| 762 | 16956886 | Observations that sulfonylureas also reverse trafficking defects caused by neonatal diabetes-associated Kir6.2 mutations in a way that is dependent on intact sulfonylurea binding sites in SUR1 further support this notion. |
| 763 | 16956886 | Reduced K(ATP) channel expression caused by mutations in the channel proteins: sulfonylurea receptor 1 (SUR1) and Kir6.2, results in loss of channel function as seen in congenital hyperinsulinism. |
| 764 | 16956886 | Interestingly, rescue of the trafficking defects requires mutant SUR1 to be co-expressed with Kir6.2, suggesting that the channel complex, rather than SUR1 alone, is the drug target. |
| 765 | 16956886 | Observations that sulfonylureas also reverse trafficking defects caused by neonatal diabetes-associated Kir6.2 mutations in a way that is dependent on intact sulfonylurea binding sites in SUR1 further support this notion. |
| 766 | 17003348 | However, in the context of beta-cells from sulfonylurea receptor 1 (SUR1) knockout mice, TIRF images showed that only mitiglinide, but not glibenclamide, caused fusion of newcomer insulin granules. |
| 767 | 17021801 | ATP-sensitive potassium (K(ATP)) channels, composed of pore-forming Kir6.2 and regulatory sulphonylurea receptor (SUR) subunits, play an essential role in insulin secretion from pancreatic beta cells. |
| 768 | 17021801 | Binding of ATP to Kir6.2 inhibits, whereas interaction of Mg-nucleotides with SUR, activates the channel. |
| 769 | 17021801 | K(ATP) channels were expressed in Xenopus oocytes and the heterozygous state was simulated by coexpression of wild-type and mutant Kir6.2 with SUR1 (the beta cell type of SUR). |
| 770 | 17021801 | ATP-sensitive potassium (K(ATP)) channels, composed of pore-forming Kir6.2 and regulatory sulphonylurea receptor (SUR) subunits, play an essential role in insulin secretion from pancreatic beta cells. |
| 771 | 17021801 | Binding of ATP to Kir6.2 inhibits, whereas interaction of Mg-nucleotides with SUR, activates the channel. |
| 772 | 17021801 | K(ATP) channels were expressed in Xenopus oocytes and the heterozygous state was simulated by coexpression of wild-type and mutant Kir6.2 with SUR1 (the beta cell type of SUR). |
| 773 | 17021801 | ATP-sensitive potassium (K(ATP)) channels, composed of pore-forming Kir6.2 and regulatory sulphonylurea receptor (SUR) subunits, play an essential role in insulin secretion from pancreatic beta cells. |
| 774 | 17021801 | Binding of ATP to Kir6.2 inhibits, whereas interaction of Mg-nucleotides with SUR, activates the channel. |
| 775 | 17021801 | K(ATP) channels were expressed in Xenopus oocytes and the heterozygous state was simulated by coexpression of wild-type and mutant Kir6.2 with SUR1 (the beta cell type of SUR). |
| 776 | 17186387 | It has resulted in great challenges for researchers elucidating the aetiology of diabetes and related features in other organ systems, for clinicians specifying a diagnosis that leads to improved genetic counselling, predicting of clinical course and changes in treatment, and for patients to altered treatment that has lead to coming off insulin and injections with no alternative (Glucokinase mutations), insulin injections being replaced by tablets (e.g. low dose in HNFalpha or high dose in potassium channel defects -Kir6.2 and SUR1) or with tablets in addition to insulin (e.g. metformin in insulin resistant syndromes). |
| 777 | 17213273 | Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers. |
| 778 | 17296510 | These channels are octameric complex with two kind of subunits: four regulatory sulfonylurea receptor (SUR) embracing four poreforming inwardly rectifying potassium channel (Kir). |
| 779 | 17296510 | Several isoforms exist for each type of subunits: SUR1 is found in the pancreatic beta-cell and neurons, whereas SUR2A is in heart cells and SUR2B in smooth muscle; Kir6.2 is in the majority of tissues as pancreatic beta-cells, brain, heart and skeletal muscle, and Kir6.1 can be found in smooth vascular muscle and astrocytes. |
| 780 | 17296510 | Sulfonylureas close K(ATP) channels by binding with high affinity to SUR suggesting they could replace insulin in these patients. |
| 781 | 17296510 | Subsequently, more than 50 patients have been reported as successfully and safely switched from subcutaneous insulin injections to oral sulfonylurea therapy, with an improvement in their glycated hemoglobin. |
| 782 | 17296510 | We therefore designed a protocol to transfer and evaluate children who have insulin treated neonatal diabetes due to KCNJ11 mutation, from insulin to sulfonylurea. |
| 783 | 17296510 | These channels are octameric complex with two kind of subunits: four regulatory sulfonylurea receptor (SUR) embracing four poreforming inwardly rectifying potassium channel (Kir). |
| 784 | 17296510 | Several isoforms exist for each type of subunits: SUR1 is found in the pancreatic beta-cell and neurons, whereas SUR2A is in heart cells and SUR2B in smooth muscle; Kir6.2 is in the majority of tissues as pancreatic beta-cells, brain, heart and skeletal muscle, and Kir6.1 can be found in smooth vascular muscle and astrocytes. |
| 785 | 17296510 | Sulfonylureas close K(ATP) channels by binding with high affinity to SUR suggesting they could replace insulin in these patients. |
| 786 | 17296510 | Subsequently, more than 50 patients have been reported as successfully and safely switched from subcutaneous insulin injections to oral sulfonylurea therapy, with an improvement in their glycated hemoglobin. |
| 787 | 17296510 | We therefore designed a protocol to transfer and evaluate children who have insulin treated neonatal diabetes due to KCNJ11 mutation, from insulin to sulfonylurea. |
| 788 | 17296510 | These channels are octameric complex with two kind of subunits: four regulatory sulfonylurea receptor (SUR) embracing four poreforming inwardly rectifying potassium channel (Kir). |
| 789 | 17296510 | Several isoforms exist for each type of subunits: SUR1 is found in the pancreatic beta-cell and neurons, whereas SUR2A is in heart cells and SUR2B in smooth muscle; Kir6.2 is in the majority of tissues as pancreatic beta-cells, brain, heart and skeletal muscle, and Kir6.1 can be found in smooth vascular muscle and astrocytes. |
| 790 | 17296510 | Sulfonylureas close K(ATP) channels by binding with high affinity to SUR suggesting they could replace insulin in these patients. |
| 791 | 17296510 | Subsequently, more than 50 patients have been reported as successfully and safely switched from subcutaneous insulin injections to oral sulfonylurea therapy, with an improvement in their glycated hemoglobin. |
| 792 | 17296510 | We therefore designed a protocol to transfer and evaluate children who have insulin treated neonatal diabetes due to KCNJ11 mutation, from insulin to sulfonylurea. |
| 793 | 17327429 | PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic beta-cells. |
| 794 | 17327429 | Transgenic mice with beta-cell-specific overexpression of ped/pea-15 (beta-tg) exhibited decreased glucose tolerance but were not insulin resistant. |
| 795 | 17327429 | Islets from the beta-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets. |
| 796 | 17327429 | Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-zeta by glucose in mouse islets and in beta-cells of the MIN-6 and INS-1 lines. |
| 797 | 17327429 | Rescue of PKC-zeta activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing beta-cells. |
| 798 | 17327429 | Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-zeta by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion. |
| 799 | 17327429 | In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic beta-cells. |
| 800 | 17327429 | PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic beta-cells. |
| 801 | 17327429 | Transgenic mice with beta-cell-specific overexpression of ped/pea-15 (beta-tg) exhibited decreased glucose tolerance but were not insulin resistant. |
| 802 | 17327429 | Islets from the beta-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets. |
| 803 | 17327429 | Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-zeta by glucose in mouse islets and in beta-cells of the MIN-6 and INS-1 lines. |
| 804 | 17327429 | Rescue of PKC-zeta activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing beta-cells. |
| 805 | 17327429 | Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-zeta by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion. |
| 806 | 17327429 | In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic beta-cells. |
| 807 | 17327429 | PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic beta-cells. |
| 808 | 17327429 | Transgenic mice with beta-cell-specific overexpression of ped/pea-15 (beta-tg) exhibited decreased glucose tolerance but were not insulin resistant. |
| 809 | 17327429 | Islets from the beta-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets. |
| 810 | 17327429 | Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-zeta by glucose in mouse islets and in beta-cells of the MIN-6 and INS-1 lines. |
| 811 | 17327429 | Rescue of PKC-zeta activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing beta-cells. |
| 812 | 17327429 | Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-zeta by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion. |
| 813 | 17327429 | In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic beta-cells. |
| 814 | 17349054 | Among these, the very recently elucidated mutations in the KCNJ11 and ABCC8 genes, encoding the Kir6.2 and SUR1 subunit of the pancreatic KATP channel involved in regulation of insulin secretion, account for one third to half of the PNDM cases. |
| 815 | 17349054 | Molecular analysis of chromosome 6 anomalies (found in more than 60% in TNDM), and the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1, provides a tool to identify TNDM from PNDM in the neonatal period. |
| 816 | 17349054 | This analysis also has potentially important therapeutic consequences leading to transfer some patients, those with mutations in KCNJ11 and ABCC8 genes, from insulin therapy to sulfonylureas. |
| 817 | 17349054 | Among these, the very recently elucidated mutations in the KCNJ11 and ABCC8 genes, encoding the Kir6.2 and SUR1 subunit of the pancreatic KATP channel involved in regulation of insulin secretion, account for one third to half of the PNDM cases. |
| 818 | 17349054 | Molecular analysis of chromosome 6 anomalies (found in more than 60% in TNDM), and the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1, provides a tool to identify TNDM from PNDM in the neonatal period. |
| 819 | 17349054 | This analysis also has potentially important therapeutic consequences leading to transfer some patients, those with mutations in KCNJ11 and ABCC8 genes, from insulin therapy to sulfonylureas. |
| 820 | 17349054 | Among these, the very recently elucidated mutations in the KCNJ11 and ABCC8 genes, encoding the Kir6.2 and SUR1 subunit of the pancreatic KATP channel involved in regulation of insulin secretion, account for one third to half of the PNDM cases. |
| 821 | 17349054 | Molecular analysis of chromosome 6 anomalies (found in more than 60% in TNDM), and the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1, provides a tool to identify TNDM from PNDM in the neonatal period. |
| 822 | 17349054 | This analysis also has potentially important therapeutic consequences leading to transfer some patients, those with mutations in KCNJ11 and ABCC8 genes, from insulin therapy to sulfonylureas. |
| 823 | 17378627 | Pancreatectomy may be required in severe cases, most of which result from a defect in the beta-cell KATP channel, encoded by ABCC8 and KCNJ11. |
| 824 | 17378627 | ABCC8 and KCNJ11 genes were sequenced and case histology was reviewed in 21 infants who had pancreatectomy. |
| 825 | 17378627 | Pancreatectomy may be required in severe cases, most of which result from a defect in the beta-cell KATP channel, encoded by ABCC8 and KCNJ11. |
| 826 | 17378627 | ABCC8 and KCNJ11 genes were sequenced and case histology was reviewed in 21 infants who had pancreatectomy. |
| 827 | 17389331 | Recently, we have described the novel mechanism where basal Mg-nucleotide-dependent stimulatory action of SUR1 on the Kir6.2 pore is increased. |
| 828 | 17389331 | In our present study, we identified six new heterozygous ABCC8 mutations, mainly in patients presenting the transient form of neonatal diabetes (six of eight), with a median duration of initial insulin therapy of 17 months (range 0.5-38.0). |
| 829 | 17389331 | Whereas Kir6.2 mutations are a common cause of permanent neonatal diabetes and in a few cases associate with the DEND (developmental delay, epilepsy, and neonatal diabetes) syndrome, SUR1 mutations are more frequent in transient (52%) compared with permanent (14%) neonatal diabetes cases screened for ABCC8 in our series. |
| 830 | 17389331 | Recently, we have described the novel mechanism where basal Mg-nucleotide-dependent stimulatory action of SUR1 on the Kir6.2 pore is increased. |
| 831 | 17389331 | In our present study, we identified six new heterozygous ABCC8 mutations, mainly in patients presenting the transient form of neonatal diabetes (six of eight), with a median duration of initial insulin therapy of 17 months (range 0.5-38.0). |
| 832 | 17389331 | Whereas Kir6.2 mutations are a common cause of permanent neonatal diabetes and in a few cases associate with the DEND (developmental delay, epilepsy, and neonatal diabetes) syndrome, SUR1 mutations are more frequent in transient (52%) compared with permanent (14%) neonatal diabetes cases screened for ABCC8 in our series. |
| 833 | 17389331 | Recently, we have described the novel mechanism where basal Mg-nucleotide-dependent stimulatory action of SUR1 on the Kir6.2 pore is increased. |
| 834 | 17389331 | In our present study, we identified six new heterozygous ABCC8 mutations, mainly in patients presenting the transient form of neonatal diabetes (six of eight), with a median duration of initial insulin therapy of 17 months (range 0.5-38.0). |
| 835 | 17389331 | Whereas Kir6.2 mutations are a common cause of permanent neonatal diabetes and in a few cases associate with the DEND (developmental delay, epilepsy, and neonatal diabetes) syndrome, SUR1 mutations are more frequent in transient (52%) compared with permanent (14%) neonatal diabetes cases screened for ABCC8 in our series. |
| 836 | 17395632 | The Kir6.2-F333I mutation differentially modulates KATP channels composed of SUR1 or SUR2 subunits. |
| 837 | 17395632 | The open probability of Kir6.2/SUR1 channels, or a C-terminally truncated form of Kir6.2 expressed in the absence of SUR, was unaffected by the mutation. |
| 838 | 17395632 | In the absence of Mg2+, ATP inhibition of all Kir6.2-F333I/SUR channel types was reduced, although SUR1-containing channels were reduced more than SUR2-containing channels. |
| 839 | 17395632 | These results suggest F333 is involved in differential coupling of Kir6.2 to SUR1 and SUR2. |
| 840 | 17395632 | This indicates Mg-nucleotide binding to SUR and the transduction of binding into opening of the Kir6.2 pore are unaffected by the mutation. |
| 841 | 17395632 | The data further suggest that MgATP hydrolysis by the nucleotide-binding domains of SUR1 and SUR2B, but not SUR2A, is enhanced by the F333I mutation in Kir6.2. |
| 842 | 17395632 | Taken together, our data suggest the region of the C terminus within which F333 lies is involved in more than one type of functional interaction with SUR, and that F333 interacts differentially with SUR1 and SUR2. |
| 843 | 17395632 | The Kir6.2-F333I mutation differentially modulates KATP channels composed of SUR1 or SUR2 subunits. |
| 844 | 17395632 | The open probability of Kir6.2/SUR1 channels, or a C-terminally truncated form of Kir6.2 expressed in the absence of SUR, was unaffected by the mutation. |
| 845 | 17395632 | In the absence of Mg2+, ATP inhibition of all Kir6.2-F333I/SUR channel types was reduced, although SUR1-containing channels were reduced more than SUR2-containing channels. |
| 846 | 17395632 | These results suggest F333 is involved in differential coupling of Kir6.2 to SUR1 and SUR2. |
| 847 | 17395632 | This indicates Mg-nucleotide binding to SUR and the transduction of binding into opening of the Kir6.2 pore are unaffected by the mutation. |
| 848 | 17395632 | The data further suggest that MgATP hydrolysis by the nucleotide-binding domains of SUR1 and SUR2B, but not SUR2A, is enhanced by the F333I mutation in Kir6.2. |
| 849 | 17395632 | Taken together, our data suggest the region of the C terminus within which F333 lies is involved in more than one type of functional interaction with SUR, and that F333 interacts differentially with SUR1 and SUR2. |
| 850 | 17395632 | The Kir6.2-F333I mutation differentially modulates KATP channels composed of SUR1 or SUR2 subunits. |
| 851 | 17395632 | The open probability of Kir6.2/SUR1 channels, or a C-terminally truncated form of Kir6.2 expressed in the absence of SUR, was unaffected by the mutation. |
| 852 | 17395632 | In the absence of Mg2+, ATP inhibition of all Kir6.2-F333I/SUR channel types was reduced, although SUR1-containing channels were reduced more than SUR2-containing channels. |
| 853 | 17395632 | These results suggest F333 is involved in differential coupling of Kir6.2 to SUR1 and SUR2. |
| 854 | 17395632 | This indicates Mg-nucleotide binding to SUR and the transduction of binding into opening of the Kir6.2 pore are unaffected by the mutation. |
| 855 | 17395632 | The data further suggest that MgATP hydrolysis by the nucleotide-binding domains of SUR1 and SUR2B, but not SUR2A, is enhanced by the F333I mutation in Kir6.2. |
| 856 | 17395632 | Taken together, our data suggest the region of the C terminus within which F333 lies is involved in more than one type of functional interaction with SUR, and that F333 interacts differentially with SUR1 and SUR2. |
| 857 | 17395632 | The Kir6.2-F333I mutation differentially modulates KATP channels composed of SUR1 or SUR2 subunits. |
| 858 | 17395632 | The open probability of Kir6.2/SUR1 channels, or a C-terminally truncated form of Kir6.2 expressed in the absence of SUR, was unaffected by the mutation. |
| 859 | 17395632 | In the absence of Mg2+, ATP inhibition of all Kir6.2-F333I/SUR channel types was reduced, although SUR1-containing channels were reduced more than SUR2-containing channels. |
| 860 | 17395632 | These results suggest F333 is involved in differential coupling of Kir6.2 to SUR1 and SUR2. |
| 861 | 17395632 | This indicates Mg-nucleotide binding to SUR and the transduction of binding into opening of the Kir6.2 pore are unaffected by the mutation. |
| 862 | 17395632 | The data further suggest that MgATP hydrolysis by the nucleotide-binding domains of SUR1 and SUR2B, but not SUR2A, is enhanced by the F333I mutation in Kir6.2. |
| 863 | 17395632 | Taken together, our data suggest the region of the C terminus within which F333 lies is involved in more than one type of functional interaction with SUR, and that F333 interacts differentially with SUR1 and SUR2. |
| 864 | 17395632 | The Kir6.2-F333I mutation differentially modulates KATP channels composed of SUR1 or SUR2 subunits. |
| 865 | 17395632 | The open probability of Kir6.2/SUR1 channels, or a C-terminally truncated form of Kir6.2 expressed in the absence of SUR, was unaffected by the mutation. |
| 866 | 17395632 | In the absence of Mg2+, ATP inhibition of all Kir6.2-F333I/SUR channel types was reduced, although SUR1-containing channels were reduced more than SUR2-containing channels. |
| 867 | 17395632 | These results suggest F333 is involved in differential coupling of Kir6.2 to SUR1 and SUR2. |
| 868 | 17395632 | This indicates Mg-nucleotide binding to SUR and the transduction of binding into opening of the Kir6.2 pore are unaffected by the mutation. |
| 869 | 17395632 | The data further suggest that MgATP hydrolysis by the nucleotide-binding domains of SUR1 and SUR2B, but not SUR2A, is enhanced by the F333I mutation in Kir6.2. |
| 870 | 17395632 | Taken together, our data suggest the region of the C terminus within which F333 lies is involved in more than one type of functional interaction with SUR, and that F333 interacts differentially with SUR1 and SUR2. |
| 871 | 17395632 | The Kir6.2-F333I mutation differentially modulates KATP channels composed of SUR1 or SUR2 subunits. |
| 872 | 17395632 | The open probability of Kir6.2/SUR1 channels, or a C-terminally truncated form of Kir6.2 expressed in the absence of SUR, was unaffected by the mutation. |
| 873 | 17395632 | In the absence of Mg2+, ATP inhibition of all Kir6.2-F333I/SUR channel types was reduced, although SUR1-containing channels were reduced more than SUR2-containing channels. |
| 874 | 17395632 | These results suggest F333 is involved in differential coupling of Kir6.2 to SUR1 and SUR2. |
| 875 | 17395632 | This indicates Mg-nucleotide binding to SUR and the transduction of binding into opening of the Kir6.2 pore are unaffected by the mutation. |
| 876 | 17395632 | The data further suggest that MgATP hydrolysis by the nucleotide-binding domains of SUR1 and SUR2B, but not SUR2A, is enhanced by the F333I mutation in Kir6.2. |
| 877 | 17395632 | Taken together, our data suggest the region of the C terminus within which F333 lies is involved in more than one type of functional interaction with SUR, and that F333 interacts differentially with SUR1 and SUR2. |
| 878 | 17395632 | The Kir6.2-F333I mutation differentially modulates KATP channels composed of SUR1 or SUR2 subunits. |
| 879 | 17395632 | The open probability of Kir6.2/SUR1 channels, or a C-terminally truncated form of Kir6.2 expressed in the absence of SUR, was unaffected by the mutation. |
| 880 | 17395632 | In the absence of Mg2+, ATP inhibition of all Kir6.2-F333I/SUR channel types was reduced, although SUR1-containing channels were reduced more than SUR2-containing channels. |
| 881 | 17395632 | These results suggest F333 is involved in differential coupling of Kir6.2 to SUR1 and SUR2. |
| 882 | 17395632 | This indicates Mg-nucleotide binding to SUR and the transduction of binding into opening of the Kir6.2 pore are unaffected by the mutation. |
| 883 | 17395632 | The data further suggest that MgATP hydrolysis by the nucleotide-binding domains of SUR1 and SUR2B, but not SUR2A, is enhanced by the F333I mutation in Kir6.2. |
| 884 | 17395632 | Taken together, our data suggest the region of the C terminus within which F333 lies is involved in more than one type of functional interaction with SUR, and that F333 interacts differentially with SUR1 and SUR2. |
| 885 | 17409272 | Although both compounds do not have a sulfonylurea structure, it has been postulated that insulin secretion is preceded by their binding to Kir6.2/SUR1 complex, and a mechanism of insulin secretion of glinides has been accounted for by this pathway. |
| 886 | 17431820 | One of them is the cardiac ATP-sensitive potassium channel (K(ATP)), which is an octamer composed of four pore-forming inwardly rectifying potassium-channel subunits (Kir6.2) and four regulatory sulfonylurea-receptor subunits (SUR2A). |
| 887 | 17446535 | In patients in whom no abnormality was identified, the KCNJ11 gene and/or ABCC8 gene, which encode the Kir6.2 and SUR1 subunits of the pancreatic beta-cell K(ATP) channel, were sequenced. |
| 888 | 17446535 | K(ATP) channel mutations were found in 25 of 97 (26%) TNDM probands (12 KCNJ11 and 13 ABCC8), while 69 of 97 (71%) had chromosome 6q24 abnormalities. |
| 889 | 17446535 | The phenotype associated with KCNJ11 and ABCC8 mutations was similar but markedly different from 6q24 patients who had a lower birth weight and who were diagnosed and remitted earlier (all P < 0.001). |
| 890 | 17446535 | In patients in whom no abnormality was identified, the KCNJ11 gene and/or ABCC8 gene, which encode the Kir6.2 and SUR1 subunits of the pancreatic beta-cell K(ATP) channel, were sequenced. |
| 891 | 17446535 | K(ATP) channel mutations were found in 25 of 97 (26%) TNDM probands (12 KCNJ11 and 13 ABCC8), while 69 of 97 (71%) had chromosome 6q24 abnormalities. |
| 892 | 17446535 | The phenotype associated with KCNJ11 and ABCC8 mutations was similar but markedly different from 6q24 patients who had a lower birth weight and who were diagnosed and remitted earlier (all P < 0.001). |
| 893 | 17446535 | In patients in whom no abnormality was identified, the KCNJ11 gene and/or ABCC8 gene, which encode the Kir6.2 and SUR1 subunits of the pancreatic beta-cell K(ATP) channel, were sequenced. |
| 894 | 17446535 | K(ATP) channel mutations were found in 25 of 97 (26%) TNDM probands (12 KCNJ11 and 13 ABCC8), while 69 of 97 (71%) had chromosome 6q24 abnormalities. |
| 895 | 17446535 | The phenotype associated with KCNJ11 and ABCC8 mutations was similar but markedly different from 6q24 patients who had a lower birth weight and who were diagnosed and remitted earlier (all P < 0.001). |
| 896 | 17496234 | The actions of a novel potent islet beta-cell specific ATP-sensitive K+ channel opener can be modulated by syntaxin-1A acting on sulfonylurea receptor 1. |
| 897 | 17496234 | We reported that syntaxin-1A binds nucleotide binding folds of sulfonylurea receptor 1 (SUR1) in beta-cells to inhibit K(ATP) channels. |
| 898 | 17496234 | Whole-cell and inside-out patch-clamp electrophysiology was used to examine the effects of glutathione S-transferase (GST)-syntaxin-1A dialysis or green fluorescence protein/syntaxin-1A cotransfection on NNC55-0462 actions. |
| 899 | 17496234 | Dialysis of GST-syntaxin-1A into the cell cytoplasm reduced both potency and efficacy of extracellularly perfused NNC55-0462 in a HEK cell line stably expressing Kir6.2/SUR1 (BA8 cells) and in rat islet beta-cells. |
| 900 | 17496234 | Moreover, inside-out membrane patches excised from BA8 cells showed that both GST-syntaxin-1A and its H3 domain inhibited K(ATP) channels previously activated by NNC55-0462. |
| 901 | 17496234 | This action on K(ATP) channels is isoform-specific to syntaxin-1A because syntaxin-2 was without effect. |
| 902 | 17496234 | Furthermore, the parent compound diazoxide showed similar sensitivity to GST-syntaxin-1A inhibition. |
| 903 | 17496234 | The actions of a novel potent islet beta-cell specific ATP-sensitive K+ channel opener can be modulated by syntaxin-1A acting on sulfonylurea receptor 1. |
| 904 | 17496234 | We reported that syntaxin-1A binds nucleotide binding folds of sulfonylurea receptor 1 (SUR1) in beta-cells to inhibit K(ATP) channels. |
| 905 | 17496234 | Whole-cell and inside-out patch-clamp electrophysiology was used to examine the effects of glutathione S-transferase (GST)-syntaxin-1A dialysis or green fluorescence protein/syntaxin-1A cotransfection on NNC55-0462 actions. |
| 906 | 17496234 | Dialysis of GST-syntaxin-1A into the cell cytoplasm reduced both potency and efficacy of extracellularly perfused NNC55-0462 in a HEK cell line stably expressing Kir6.2/SUR1 (BA8 cells) and in rat islet beta-cells. |
| 907 | 17496234 | Moreover, inside-out membrane patches excised from BA8 cells showed that both GST-syntaxin-1A and its H3 domain inhibited K(ATP) channels previously activated by NNC55-0462. |
| 908 | 17496234 | This action on K(ATP) channels is isoform-specific to syntaxin-1A because syntaxin-2 was without effect. |
| 909 | 17496234 | Furthermore, the parent compound diazoxide showed similar sensitivity to GST-syntaxin-1A inhibition. |
| 910 | 17496234 | The actions of a novel potent islet beta-cell specific ATP-sensitive K+ channel opener can be modulated by syntaxin-1A acting on sulfonylurea receptor 1. |
| 911 | 17496234 | We reported that syntaxin-1A binds nucleotide binding folds of sulfonylurea receptor 1 (SUR1) in beta-cells to inhibit K(ATP) channels. |
| 912 | 17496234 | Whole-cell and inside-out patch-clamp electrophysiology was used to examine the effects of glutathione S-transferase (GST)-syntaxin-1A dialysis or green fluorescence protein/syntaxin-1A cotransfection on NNC55-0462 actions. |
| 913 | 17496234 | Dialysis of GST-syntaxin-1A into the cell cytoplasm reduced both potency and efficacy of extracellularly perfused NNC55-0462 in a HEK cell line stably expressing Kir6.2/SUR1 (BA8 cells) and in rat islet beta-cells. |
| 914 | 17496234 | Moreover, inside-out membrane patches excised from BA8 cells showed that both GST-syntaxin-1A and its H3 domain inhibited K(ATP) channels previously activated by NNC55-0462. |
| 915 | 17496234 | This action on K(ATP) channels is isoform-specific to syntaxin-1A because syntaxin-2 was without effect. |
| 916 | 17496234 | Furthermore, the parent compound diazoxide showed similar sensitivity to GST-syntaxin-1A inhibition. |
| 917 | 17522344 | Finally, iptakalim inhibited Kir6.2/SUR1, but it activated Kir6.1/SUR2B (vascular-type), K(ATP) channels heterologously expressed in Xenopus oocytes. |
| 918 | 17535866 | Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes. |
| 919 | 17575084 | Mutations in the pancreatic ATP-sensitive K(+) (K(ATP)) channel proteins sulfonylurea receptor 1 (SUR1) and Kir6.2, encoded by ABCC8 and KCNJ11, respectively, is the most common cause of the disease. |
| 920 | 17584766 | Activating mutations in the genes encoding the ATP-sensitive potassium (K(ATP)) channel subunits Kir6.2 and SUR1 are a common cause of neonatal diabetes. |
| 921 | 17584766 | They also provide further evidence that interactions between TMD0 of SUR1 and Kir6.2 are critical for K(ATP) channel gating and identify a residue crucial for this interaction at both physical and functional levels. |
| 922 | 17584766 | Activating mutations in the genes encoding the ATP-sensitive potassium (K(ATP)) channel subunits Kir6.2 and SUR1 are a common cause of neonatal diabetes. |
| 923 | 17584766 | They also provide further evidence that interactions between TMD0 of SUR1 and Kir6.2 are critical for K(ATP) channel gating and identify a residue crucial for this interaction at both physical and functional levels. |
| 924 | 17666135 | KATP channels are made up of four subunits each of Kir6.2 and the sulphonylurea receptor (SUR1), encoded by the genes KCNJ11 and ABCC8, respectively. |
| 925 | 17701889 | The effects of NN414, a SUR1/Kir6.2 selective potassium channel opener in subjects with type 2 diabetes. |
| 926 | 17823772 | We found significant associations between eight SNPs, including the KCNJ11 E23K and ABCC8 S1369A variants, and T2D. |
| 927 | 17919178 | K(ATP) channels were expressed in Xenopus oocytes, and the heterozygous state was simulated by coexpression of wild-type and mutant Kir6.2 with SUR1 (the beta cell type of sulphonylurea receptor (SUR)). |
| 928 | 17919178 | The E322K mutation was without effect when Kir6.2 was expressed in the absence of SUR1, suggesting that this residue impairs coupling to SUR1. |
| 929 | 17919178 | K(ATP) channels were expressed in Xenopus oocytes, and the heterozygous state was simulated by coexpression of wild-type and mutant Kir6.2 with SUR1 (the beta cell type of sulphonylurea receptor (SUR)). |
| 930 | 17919178 | The E322K mutation was without effect when Kir6.2 was expressed in the absence of SUR1, suggesting that this residue impairs coupling to SUR1. |
| 931 | 17919182 | Consistent with this paradigm, loss-of-function mutations in the genes (KCNJ11 and ABCC8) that encode the two subunits (Kir6.2 and SUR1, respectively) of the ATP-sensitive K(+) (K(ATP)) channel underlie hyperinsulinism in humans, a genetic disorder characterized by dysregulated insulin secretion. |
| 932 | 17923772 | These channels are octameric complexes of 4 pore-forming Kir and 4 regulatory sulphonylurea receptor (SUR) subunits. |
| 933 | 17923772 | In vitro studies showed no attenuation of ATP sensitivity but an increase in the opening probability of the channel through interaction of the mutated SUR1 subunit on Kir6.2. |
| 934 | 17923772 | Sulphonylureas close KATP channels by binding with high affinity to SUR suggesting they could replace insulin in these patients. |
| 935 | 17923772 | Subsequently, more than 60 patients have been reported as successfully switched from insulin subcutaneous injections to oral sulphonylurea therapy, with an improvement in their glycated hemoglobin. |
| 936 | 17923772 | These channels are octameric complexes of 4 pore-forming Kir and 4 regulatory sulphonylurea receptor (SUR) subunits. |
| 937 | 17923772 | In vitro studies showed no attenuation of ATP sensitivity but an increase in the opening probability of the channel through interaction of the mutated SUR1 subunit on Kir6.2. |
| 938 | 17923772 | Sulphonylureas close KATP channels by binding with high affinity to SUR suggesting they could replace insulin in these patients. |
| 939 | 17923772 | Subsequently, more than 60 patients have been reported as successfully switched from insulin subcutaneous injections to oral sulphonylurea therapy, with an improvement in their glycated hemoglobin. |
| 940 | 17923772 | These channels are octameric complexes of 4 pore-forming Kir and 4 regulatory sulphonylurea receptor (SUR) subunits. |
| 941 | 17923772 | In vitro studies showed no attenuation of ATP sensitivity but an increase in the opening probability of the channel through interaction of the mutated SUR1 subunit on Kir6.2. |
| 942 | 17923772 | Sulphonylureas close KATP channels by binding with high affinity to SUR suggesting they could replace insulin in these patients. |
| 943 | 17923772 | Subsequently, more than 60 patients have been reported as successfully switched from insulin subcutaneous injections to oral sulphonylurea therapy, with an improvement in their glycated hemoglobin. |
| 944 | 17931842 | Among those, the very recently elucidated mutations in KCNJ11 and ABCC8 gene, encoding the Kir6.2 and SUR1 subunit of the pancreatic K(ATP) channel involved in regulation of insulin secretion accounts for one third to a half of the PNDM cases. |
| 945 | 17931842 | Molecular analysis of chromosome 6 anomalies, the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1 provide a tool to identify transient from permanent neonatal diabetes mellitus in the neonatal period. |
| 946 | 17931842 | This analysis also has potentially important therapeutic consequences leading to transfer some patients, those with mutations in KCNJ11 and ABCC8 from insulin therapy to sulfonylureas. |
| 947 | 17931842 | Among those, the very recently elucidated mutations in KCNJ11 and ABCC8 gene, encoding the Kir6.2 and SUR1 subunit of the pancreatic K(ATP) channel involved in regulation of insulin secretion accounts for one third to a half of the PNDM cases. |
| 948 | 17931842 | Molecular analysis of chromosome 6 anomalies, the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1 provide a tool to identify transient from permanent neonatal diabetes mellitus in the neonatal period. |
| 949 | 17931842 | This analysis also has potentially important therapeutic consequences leading to transfer some patients, those with mutations in KCNJ11 and ABCC8 from insulin therapy to sulfonylureas. |
| 950 | 17931842 | Among those, the very recently elucidated mutations in KCNJ11 and ABCC8 gene, encoding the Kir6.2 and SUR1 subunit of the pancreatic K(ATP) channel involved in regulation of insulin secretion accounts for one third to a half of the PNDM cases. |
| 951 | 17931842 | Molecular analysis of chromosome 6 anomalies, the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1 provide a tool to identify transient from permanent neonatal diabetes mellitus in the neonatal period. |
| 952 | 17931842 | This analysis also has potentially important therapeutic consequences leading to transfer some patients, those with mutations in KCNJ11 and ABCC8 from insulin therapy to sulfonylureas. |
| 953 | 18025464 | Gain-of-function mutations in the genes encoding the ATP-sensitive potassium (K(ATP)) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) are a common cause of neonatal diabetes mellitus. |
| 954 | 18025464 | SUR1 is a channel regulator that modulates the gating of the pore formed by Kir6.2. |
| 955 | 18025464 | K(ATP) channel activity is inhibited by ATP binding to Kir6.2 but is stimulated by MgADP binding, or by MgATP binding and hydrolysis, at the NBDs of SUR1. |
| 956 | 18025464 | Gain-of-function mutations in the genes encoding the ATP-sensitive potassium (K(ATP)) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) are a common cause of neonatal diabetes mellitus. |
| 957 | 18025464 | SUR1 is a channel regulator that modulates the gating of the pore formed by Kir6.2. |
| 958 | 18025464 | K(ATP) channel activity is inhibited by ATP binding to Kir6.2 but is stimulated by MgADP binding, or by MgATP binding and hydrolysis, at the NBDs of SUR1. |
| 959 | 18025464 | Gain-of-function mutations in the genes encoding the ATP-sensitive potassium (K(ATP)) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) are a common cause of neonatal diabetes mellitus. |
| 960 | 18025464 | SUR1 is a channel regulator that modulates the gating of the pore formed by Kir6.2. |
| 961 | 18025464 | K(ATP) channel activity is inhibited by ATP binding to Kir6.2 but is stimulated by MgADP binding, or by MgATP binding and hydrolysis, at the NBDs of SUR1. |
| 962 | 18281290 | ATP/ADP-sensing (sulfonylurea receptor (SUR)/K(IR)6)(4) K(ATP) channels regulate the excitability of our insulin secreting and other vital cells via the differential MgATP/ADP-dependent stimulatory actions of their tissue-specific ATP-binding cassette regulatory subunits (sulfonylurea receptors), which counterbalance the nearly constant inhibitory action of ATP on the K(+) inwardly rectifying pore. |
| 963 | 18301398 | Firstly, diabetes diagnosed before 6 months of age frequently results from mutation of genes that encode Kir6.2 (ATP-sensitive inward rectifier potassium channel) or sulfonylurea receptor 1 subunits of an ATP-sensitive potassium channel, and improved glycemic control can be achieved by treatment with high-dose sulfonylureas rather than insulin. |
| 964 | 18323694 | They are composed of two types of subunits; the pore subunits (Kir6.1, Kir6.2), which are members of the inwardly rectifying K+ channel family, and the regulatory subunits, the sulphonylurea receptors, which belong to the ATP-binding cassette (ABC) superfamily. |
| 965 | 18323694 | The SURs are divided into two isoforms, SUR1 and SUR2, the latter was further divided into SUR2A and SUR2B. |
| 966 | 18378016 | Islet Neogenesis Associated Protein (INGAP) increases pancreatic beta-cell mass and potentiates glucose-induced insulin secretion. |
| 967 | 18378016 | Thereafter, gene (RT-PCR) and protein expression (Western blotting) of Foxa2, SUR1 and Kir6.2, cytoplasmic Ca(2+) ([Ca(2+)](i)), static and dynamic insulin secretion, and (86)Rb efflux were measured. |
| 968 | 18378016 | INGAP-PP increased the expression levels of Kir6.2, SUR1 and Foxa2 genes, and SUR1 and Foxa2 proteins. |
| 969 | 18378016 | Islet Neogenesis Associated Protein (INGAP) increases pancreatic beta-cell mass and potentiates glucose-induced insulin secretion. |
| 970 | 18378016 | Thereafter, gene (RT-PCR) and protein expression (Western blotting) of Foxa2, SUR1 and Kir6.2, cytoplasmic Ca(2+) ([Ca(2+)](i)), static and dynamic insulin secretion, and (86)Rb efflux were measured. |
| 971 | 18378016 | INGAP-PP increased the expression levels of Kir6.2, SUR1 and Foxa2 genes, and SUR1 and Foxa2 proteins. |
| 972 | 18497752 | Activating mutations in the pore-forming Kir6.2 (KCNJ11) and regulatory sulphonylurea receptor SUR1 (ABCC8) subunits of the K(ATP) channel are a common cause of transient neonatal diabetes mellitus (TNDM). |
| 973 | 18512226 | We sequenced genes with a recognized role in monogenic forms of diabetes, including KCNJ11, ABCC8, GCK, IPF1, HNF1beta, NeuroD1 and TCF7L2, as well as a novel candidate gene, HNF6, known to be involved in hepatobiliary and pancreatic development, but did not identify mutations. |
| 974 | 18758683 | The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by beta-cells and hence could be involved in the pathogenesis of type 2 diabetes (T2D). |
| 975 | 18758683 | The KCNJ11 E23K and ABCC8 exon 31 variants have been studied in 127 Russian T2D patients and 117 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. |
| 976 | 18758683 | The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with higher risk of T2D [Odds ratio (OR) of 1.53 (P=0.023) and 2.41 (P=1.95 x 10(-5))], respectively. |
| 977 | 18758683 | The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in diabetic and non-diabetic patients. |
| 978 | 18758683 | The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population. |
| 979 | 18758683 | The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by beta-cells and hence could be involved in the pathogenesis of type 2 diabetes (T2D). |
| 980 | 18758683 | The KCNJ11 E23K and ABCC8 exon 31 variants have been studied in 127 Russian T2D patients and 117 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. |
| 981 | 18758683 | The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with higher risk of T2D [Odds ratio (OR) of 1.53 (P=0.023) and 2.41 (P=1.95 x 10(-5))], respectively. |
| 982 | 18758683 | The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in diabetic and non-diabetic patients. |
| 983 | 18758683 | The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population. |
| 984 | 18758683 | The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by beta-cells and hence could be involved in the pathogenesis of type 2 diabetes (T2D). |
| 985 | 18758683 | The KCNJ11 E23K and ABCC8 exon 31 variants have been studied in 127 Russian T2D patients and 117 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. |
| 986 | 18758683 | The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with higher risk of T2D [Odds ratio (OR) of 1.53 (P=0.023) and 2.41 (P=1.95 x 10(-5))], respectively. |
| 987 | 18758683 | The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in diabetic and non-diabetic patients. |
| 988 | 18758683 | The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population. |
| 989 | 18758683 | The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by beta-cells and hence could be involved in the pathogenesis of type 2 diabetes (T2D). |
| 990 | 18758683 | The KCNJ11 E23K and ABCC8 exon 31 variants have been studied in 127 Russian T2D patients and 117 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. |
| 991 | 18758683 | The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with higher risk of T2D [Odds ratio (OR) of 1.53 (P=0.023) and 2.41 (P=1.95 x 10(-5))], respectively. |
| 992 | 18758683 | The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in diabetic and non-diabetic patients. |
| 993 | 18758683 | The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population. |
| 994 | 18758683 | The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by beta-cells and hence could be involved in the pathogenesis of type 2 diabetes (T2D). |
| 995 | 18758683 | The KCNJ11 E23K and ABCC8 exon 31 variants have been studied in 127 Russian T2D patients and 117 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. |
| 996 | 18758683 | The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with higher risk of T2D [Odds ratio (OR) of 1.53 (P=0.023) and 2.41 (P=1.95 x 10(-5))], respectively. |
| 997 | 18758683 | The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in diabetic and non-diabetic patients. |
| 998 | 18758683 | The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population. |
| 999 | 18767144 | Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism. |
| 1000 | 18767144 | The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1 (SUR1). |
| 1001 | 18767144 | It has been known for some time that loss of function mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1, can cause oversecretion of insulin and result in hyperinsulinism of infancy, while activating mutations in KCNJ11 and ABCC8 have recently been described that result in the opposite phenotype of diabetes. |
| 1002 | 18767144 | Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism. |
| 1003 | 18767144 | The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1 (SUR1). |
| 1004 | 18767144 | It has been known for some time that loss of function mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1, can cause oversecretion of insulin and result in hyperinsulinism of infancy, while activating mutations in KCNJ11 and ABCC8 have recently been described that result in the opposite phenotype of diabetes. |
| 1005 | 18767144 | Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism. |
| 1006 | 18767144 | The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1 (SUR1). |
| 1007 | 18767144 | It has been known for some time that loss of function mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1, can cause oversecretion of insulin and result in hyperinsulinism of infancy, while activating mutations in KCNJ11 and ABCC8 have recently been described that result in the opposite phenotype of diabetes. |
| 1008 | 18990670 | The ATP-sensitive (KATP) channel is an octameric complex of four pore-forming Kir6.2 subunits and four regulatory SUR1 subunits, and it links cell metabolism to electrical activity in many cell types. |
| 1009 | 18990670 | Precisely how SUR1 talks to Kir6.2 remains unclear, but recent studies have identified some residues and domains that are involved in both physical and functional interactions between the two proteins. |
| 1010 | 18990670 | The importance of these interactions is exemplified by the fact that impaired regulation of Kir6.2 by SUR1 results in human disease, with loss-of-function SUR1 mutations causing congenital hyperinsulinism and gain-of-function SUR1 mutations leading to neonatal diabetes. |
| 1011 | 18990670 | This paper reviews recent data on the regulation of Kir6.2 by SUR1 and considers the molecular mechanisms by which SUR1 mutations produce disease. |
| 1012 | 18990670 | The ATP-sensitive (KATP) channel is an octameric complex of four pore-forming Kir6.2 subunits and four regulatory SUR1 subunits, and it links cell metabolism to electrical activity in many cell types. |
| 1013 | 18990670 | Precisely how SUR1 talks to Kir6.2 remains unclear, but recent studies have identified some residues and domains that are involved in both physical and functional interactions between the two proteins. |
| 1014 | 18990670 | The importance of these interactions is exemplified by the fact that impaired regulation of Kir6.2 by SUR1 results in human disease, with loss-of-function SUR1 mutations causing congenital hyperinsulinism and gain-of-function SUR1 mutations leading to neonatal diabetes. |
| 1015 | 18990670 | This paper reviews recent data on the regulation of Kir6.2 by SUR1 and considers the molecular mechanisms by which SUR1 mutations produce disease. |
| 1016 | 18990670 | The ATP-sensitive (KATP) channel is an octameric complex of four pore-forming Kir6.2 subunits and four regulatory SUR1 subunits, and it links cell metabolism to electrical activity in many cell types. |
| 1017 | 18990670 | Precisely how SUR1 talks to Kir6.2 remains unclear, but recent studies have identified some residues and domains that are involved in both physical and functional interactions between the two proteins. |
| 1018 | 18990670 | The importance of these interactions is exemplified by the fact that impaired regulation of Kir6.2 by SUR1 results in human disease, with loss-of-function SUR1 mutations causing congenital hyperinsulinism and gain-of-function SUR1 mutations leading to neonatal diabetes. |
| 1019 | 18990670 | This paper reviews recent data on the regulation of Kir6.2 by SUR1 and considers the molecular mechanisms by which SUR1 mutations produce disease. |
| 1020 | 18990670 | The ATP-sensitive (KATP) channel is an octameric complex of four pore-forming Kir6.2 subunits and four regulatory SUR1 subunits, and it links cell metabolism to electrical activity in many cell types. |
| 1021 | 18990670 | Precisely how SUR1 talks to Kir6.2 remains unclear, but recent studies have identified some residues and domains that are involved in both physical and functional interactions between the two proteins. |
| 1022 | 18990670 | The importance of these interactions is exemplified by the fact that impaired regulation of Kir6.2 by SUR1 results in human disease, with loss-of-function SUR1 mutations causing congenital hyperinsulinism and gain-of-function SUR1 mutations leading to neonatal diabetes. |
| 1023 | 18990670 | This paper reviews recent data on the regulation of Kir6.2 by SUR1 and considers the molecular mechanisms by which SUR1 mutations produce disease. |
| 1024 | 18998097 | The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1. |
| 1025 | 18998097 | Loss of function mutations in the KCNJ11 and ABCC8 genes that encode for Kir6.2 and SUR1 can cause over-secretion of insulin and result in hyperinsulinism of infancy, while gain of function mutations in KCNJ11 and ABCC8 have recently been described that result in the opposite phenotype of diabetes.Genetic testing is important for patients with hyperinsulinism or neonatal diabetes, as identification of a K(ATP) channel mutation confirms a diagnosis of their disorder. |
| 1026 | 18998097 | The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1. |
| 1027 | 18998097 | Loss of function mutations in the KCNJ11 and ABCC8 genes that encode for Kir6.2 and SUR1 can cause over-secretion of insulin and result in hyperinsulinism of infancy, while gain of function mutations in KCNJ11 and ABCC8 have recently been described that result in the opposite phenotype of diabetes.Genetic testing is important for patients with hyperinsulinism or neonatal diabetes, as identification of a K(ATP) channel mutation confirms a diagnosis of their disorder. |
| 1028 | 19065048 | It is commonly caused by gain-of-function mutations in the genes encoding the Kir6.2 and SUR1 subunits of the plasmalemmal ATP-sensitive K+ (KATP) channel. |
| 1029 | 19065048 | Expression of the V59M Kir6.2 mutation in pancreatic beta cells alone is thus sufficient to recapitulate the neonatal diabetes observed in humans. beta-V59M islets also displayed a reduced percentage of beta cells, abnormal morphology, lower insulin content, and decreased expression of Kir6.2, SUR1, and insulin mRNA. |
| 1030 | 19065048 | It is commonly caused by gain-of-function mutations in the genes encoding the Kir6.2 and SUR1 subunits of the plasmalemmal ATP-sensitive K+ (KATP) channel. |
| 1031 | 19065048 | Expression of the V59M Kir6.2 mutation in pancreatic beta cells alone is thus sufficient to recapitulate the neonatal diabetes observed in humans. beta-V59M islets also displayed a reduced percentage of beta cells, abnormal morphology, lower insulin content, and decreased expression of Kir6.2, SUR1, and insulin mRNA. |
| 1032 | 19139106 | Analysis of two KCNJ11 neonatal diabetes mutations, V59G and V59A, and the analogous KCNJ8 I60G substitution: differences between the channel subtypes formed with SUR1. |
| 1033 | 19139106 | beta-Cell-type K(ATP) channels are octamers assembled from Kir6.2/KCNJ11 and SUR1/ABCC8. |
| 1034 | 19139106 | Nucleotide binding to Kir6.2 inhibits channel activity, whereas ATP binding/hydrolysis on sulfonylurea receptor 1 (SUR1) opposes inhibition. |
| 1035 | 19139106 | Segments of the Kir6.2 N terminus are important for open-to-closed transitions, form part of the Kir ATP, sulfonylurea, and phosphoinositide binding sites, and interact with L0, an SUR cytoplasmic loop. |
| 1036 | 19139106 | We compared Kir6.x/SUR1 channels carrying the V59G substitution, a cause of the developmental delay, epilepsy, and neonatal diabetes syndrome, with a V59A substitution and the equivalent I60G mutation in the related Kir6.1 subunit from vascular smooth muscle. |
| 1037 | 19139106 | Analysis of two KCNJ11 neonatal diabetes mutations, V59G and V59A, and the analogous KCNJ8 I60G substitution: differences between the channel subtypes formed with SUR1. |
| 1038 | 19139106 | beta-Cell-type K(ATP) channels are octamers assembled from Kir6.2/KCNJ11 and SUR1/ABCC8. |
| 1039 | 19139106 | Nucleotide binding to Kir6.2 inhibits channel activity, whereas ATP binding/hydrolysis on sulfonylurea receptor 1 (SUR1) opposes inhibition. |
| 1040 | 19139106 | Segments of the Kir6.2 N terminus are important for open-to-closed transitions, form part of the Kir ATP, sulfonylurea, and phosphoinositide binding sites, and interact with L0, an SUR cytoplasmic loop. |
| 1041 | 19139106 | We compared Kir6.x/SUR1 channels carrying the V59G substitution, a cause of the developmental delay, epilepsy, and neonatal diabetes syndrome, with a V59A substitution and the equivalent I60G mutation in the related Kir6.1 subunit from vascular smooth muscle. |
| 1042 | 19139106 | Analysis of two KCNJ11 neonatal diabetes mutations, V59G and V59A, and the analogous KCNJ8 I60G substitution: differences between the channel subtypes formed with SUR1. |
| 1043 | 19139106 | beta-Cell-type K(ATP) channels are octamers assembled from Kir6.2/KCNJ11 and SUR1/ABCC8. |
| 1044 | 19139106 | Nucleotide binding to Kir6.2 inhibits channel activity, whereas ATP binding/hydrolysis on sulfonylurea receptor 1 (SUR1) opposes inhibition. |
| 1045 | 19139106 | Segments of the Kir6.2 N terminus are important for open-to-closed transitions, form part of the Kir ATP, sulfonylurea, and phosphoinositide binding sites, and interact with L0, an SUR cytoplasmic loop. |
| 1046 | 19139106 | We compared Kir6.x/SUR1 channels carrying the V59G substitution, a cause of the developmental delay, epilepsy, and neonatal diabetes syndrome, with a V59A substitution and the equivalent I60G mutation in the related Kir6.1 subunit from vascular smooth muscle. |
| 1047 | 19139106 | Analysis of two KCNJ11 neonatal diabetes mutations, V59G and V59A, and the analogous KCNJ8 I60G substitution: differences between the channel subtypes formed with SUR1. |
| 1048 | 19139106 | beta-Cell-type K(ATP) channels are octamers assembled from Kir6.2/KCNJ11 and SUR1/ABCC8. |
| 1049 | 19139106 | Nucleotide binding to Kir6.2 inhibits channel activity, whereas ATP binding/hydrolysis on sulfonylurea receptor 1 (SUR1) opposes inhibition. |
| 1050 | 19139106 | Segments of the Kir6.2 N terminus are important for open-to-closed transitions, form part of the Kir ATP, sulfonylurea, and phosphoinositide binding sites, and interact with L0, an SUR cytoplasmic loop. |
| 1051 | 19139106 | We compared Kir6.x/SUR1 channels carrying the V59G substitution, a cause of the developmental delay, epilepsy, and neonatal diabetes syndrome, with a V59A substitution and the equivalent I60G mutation in the related Kir6.1 subunit from vascular smooth muscle. |
| 1052 | 19139106 | Analysis of two KCNJ11 neonatal diabetes mutations, V59G and V59A, and the analogous KCNJ8 I60G substitution: differences between the channel subtypes formed with SUR1. |
| 1053 | 19139106 | beta-Cell-type K(ATP) channels are octamers assembled from Kir6.2/KCNJ11 and SUR1/ABCC8. |
| 1054 | 19139106 | Nucleotide binding to Kir6.2 inhibits channel activity, whereas ATP binding/hydrolysis on sulfonylurea receptor 1 (SUR1) opposes inhibition. |
| 1055 | 19139106 | Segments of the Kir6.2 N terminus are important for open-to-closed transitions, form part of the Kir ATP, sulfonylurea, and phosphoinositide binding sites, and interact with L0, an SUR cytoplasmic loop. |
| 1056 | 19139106 | We compared Kir6.x/SUR1 channels carrying the V59G substitution, a cause of the developmental delay, epilepsy, and neonatal diabetes syndrome, with a V59A substitution and the equivalent I60G mutation in the related Kir6.1 subunit from vascular smooth muscle. |
| 1057 | 19151370 | Sulfonylurea receptor 1 mutations that cause opposite insulin secretion defects with chemical chaperone exposure. |
| 1058 | 19151370 | The beta-cell ATP-sensitive potassium (K(ATP)) channel composed of sulfonylurea receptor SUR1 and potassium channel Kir6.2 serves a key role in insulin secretion regulation by linking glucose metabolism to cell excitability. |
| 1059 | 19151370 | Mutations in SUR1 or Kir6.2 that decrease channel function are typically associated with congenital hyperinsulinism, whereas those that increase channel function are associated with neonatal diabetes. |
| 1060 | 19151370 | Further analyses revealed a nucleotide-independent decrease in mutant channel intrinsic open probability, suggesting the mutations may reduce ATP sensitivity by causing functional uncoupling between SUR1 and Kir6.2. |
| 1061 | 19151370 | Sulfonylurea receptor 1 mutations that cause opposite insulin secretion defects with chemical chaperone exposure. |
| 1062 | 19151370 | The beta-cell ATP-sensitive potassium (K(ATP)) channel composed of sulfonylurea receptor SUR1 and potassium channel Kir6.2 serves a key role in insulin secretion regulation by linking glucose metabolism to cell excitability. |
| 1063 | 19151370 | Mutations in SUR1 or Kir6.2 that decrease channel function are typically associated with congenital hyperinsulinism, whereas those that increase channel function are associated with neonatal diabetes. |
| 1064 | 19151370 | Further analyses revealed a nucleotide-independent decrease in mutant channel intrinsic open probability, suggesting the mutations may reduce ATP sensitivity by causing functional uncoupling between SUR1 and Kir6.2. |
| 1065 | 19151370 | Sulfonylurea receptor 1 mutations that cause opposite insulin secretion defects with chemical chaperone exposure. |
| 1066 | 19151370 | The beta-cell ATP-sensitive potassium (K(ATP)) channel composed of sulfonylurea receptor SUR1 and potassium channel Kir6.2 serves a key role in insulin secretion regulation by linking glucose metabolism to cell excitability. |
| 1067 | 19151370 | Mutations in SUR1 or Kir6.2 that decrease channel function are typically associated with congenital hyperinsulinism, whereas those that increase channel function are associated with neonatal diabetes. |
| 1068 | 19151370 | Further analyses revealed a nucleotide-independent decrease in mutant channel intrinsic open probability, suggesting the mutations may reduce ATP sensitivity by causing functional uncoupling between SUR1 and Kir6.2. |
| 1069 | 19151370 | Sulfonylurea receptor 1 mutations that cause opposite insulin secretion defects with chemical chaperone exposure. |
| 1070 | 19151370 | The beta-cell ATP-sensitive potassium (K(ATP)) channel composed of sulfonylurea receptor SUR1 and potassium channel Kir6.2 serves a key role in insulin secretion regulation by linking glucose metabolism to cell excitability. |
| 1071 | 19151370 | Mutations in SUR1 or Kir6.2 that decrease channel function are typically associated with congenital hyperinsulinism, whereas those that increase channel function are associated with neonatal diabetes. |
| 1072 | 19151370 | Further analyses revealed a nucleotide-independent decrease in mutant channel intrinsic open probability, suggesting the mutations may reduce ATP sensitivity by causing functional uncoupling between SUR1 and Kir6.2. |
| 1073 | 19273354 | An aetiological approach has identified monogenic patients with diabetes due to TCF1 mutations who are particularly sensitive to the hypoglycaemic effects of sulphonylureas, and KCNJ11 or ABCC8 mutations in which sulphonylureas can be used in place of insulin treatment. |
| 1074 | 19496967 | Permanent neonatal diabetes mellitus is a rare disorder known to be caused by activating mutations in KCNJ11 or ABCC8, inactivating mutations in INS, or very rarely in GCK or insulin promotor factor-1 (IPF-1) genes. |
| 1075 | 19498446 | The genes (ABCC8 and KCNJ11) have a key role in glucose-stimulated insulin secretion and thus have always been considered as excellent susceptibility candidates for involvement in type 2 diabetes. |
| 1076 | 19521719 | We identified no mutations in ZFP57, KCNJ11, ABCC8, GCK, HNF1A, HNF1B, HNF3B, IPF1, PAX4, or ZIC3. |
| 1077 | 19521719 | The proband had loss of methylation at the 6q24 locus TNDM and also at the loci IGF2R, DIRAS3, and PEG1, while the other family members, including the healthy monozygotic twin, had normal findings. |
| 1078 | 19766903 | Metabolic control in type 2 diabetes is associated with sulfonylurea receptor-1 (SUR-1) but not with KCNJ11 polymorphisms. |
| 1079 | 19799532 | CYP2C19 genotype is more influential for gliclazide pharmacokinetics when compared to CYP2C9. |
| 1080 | 19799532 | Sulfonylurea receptor 1 (SUR1, ABCC8 gene) and K+ inward rectifier Kir6.2 (KCNJ11) have been correlated to significant variation in sulfonylurea response. |
| 1081 | 19799532 | Diabetics with the SUR1 exon 33 G allele are more sensitive to gliclazide and the rs5210 variant of the KCNJ11 gene was associated with improved clinical efficacy of gliclazide. |
| 1082 | 19799532 | Carriers of Transcription factor 7-like 2 (TCF7L2) variants are more likely to fail sulfonylurea therapy. |
| 1083 | 19799532 | CYP2C19 genotype is more influential for gliclazide pharmacokinetics when compared to CYP2C9. |
| 1084 | 19799532 | Sulfonylurea receptor 1 (SUR1, ABCC8 gene) and K+ inward rectifier Kir6.2 (KCNJ11) have been correlated to significant variation in sulfonylurea response. |
| 1085 | 19799532 | Diabetics with the SUR1 exon 33 G allele are more sensitive to gliclazide and the rs5210 variant of the KCNJ11 gene was associated with improved clinical efficacy of gliclazide. |
| 1086 | 19799532 | Carriers of Transcription factor 7-like 2 (TCF7L2) variants are more likely to fail sulfonylurea therapy. |
| 1087 | 19805912 | Using mice lacking the sulfonylurea receptor type 1 (Sur1) subunit of KATP channels, we found that, compared with insulin secretion by WT islets, insulin secretion by Sur1-/- islets was less susceptible to oxidative stress induced by the oxidant H2O2. |
| 1088 | 19933268 | The function of the ATP-sensitive potassium (K(ATP)) channel relies on the proper coupling between its two subunits: the pore-forming Kir6.2 and the regulator SUR. |
| 1089 | 19933268 | The conformation of the interface between these two subunits can be monitored using a rhodamine 123 (Rho) protection assay because Rho blocks Kir6.2 with an efficiency that depends on the relative position of transmembrane domain (TMD) 0 of the associated SUR (Hosy, E., Dérand, R., Revilloud, J., and Vivaudou, M. (2007) J. |
| 1090 | 19933268 | The function of the ATP-sensitive potassium (K(ATP)) channel relies on the proper coupling between its two subunits: the pore-forming Kir6.2 and the regulator SUR. |
| 1091 | 19933268 | The conformation of the interface between these two subunits can be monitored using a rhodamine 123 (Rho) protection assay because Rho blocks Kir6.2 with an efficiency that depends on the relative position of transmembrane domain (TMD) 0 of the associated SUR (Hosy, E., Dérand, R., Revilloud, J., and Vivaudou, M. (2007) J. |
| 1092 | 20022885 | Gain-of-function mutations in the genes encoding the Kir6.2 and SUR1 subunits of this channel cause neonatal diabetes. |
| 1093 | 20033705 | Assembly of an inward rectifier K+ channel pore (Kir6.1/Kir6.2) and an adenosine triphosphate (ATP)-binding regulatory subunit (SUR1/SUR2A/SUR2B) forms ATP-sensitive K+ (KATP) channel heteromultimers, widely distributed in metabolically active tissues throughout the body. |
| 1094 | 20042013 | Several molecular mechanisms are involved in the development of CHI, but the most common genetic defects are inactivating mutations of the ABCC8 or KCNJ11 genes. |
| 1095 | 20049716 | Loss- and gain-of-function mutations in the genes encoding the Kir6.2 and SUR1 subunits of this channel cause hyperinsulinism of infancy and neonatal diabetes, respectively. |
| 1096 | 20079163 | Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population. |
| 1097 | 20082465 | Investigations included sequencing of GCK, ABCC8, IPF1, NEUROD1, PTF1A, HNF1B, INS, ISL1, NGN3, HHEX, G6PC2, TCF7L2, SOX4, FOXP3 (Patients 1 and 2), GATA4 and KCNJ11 genes (all three patients), but no mutations were found. |
| 1098 | 20099993 | The renin-angiotensin system genes, cytokine-encoding genes, and plasminogen activator inhibitor type 1 genes have been implicated in calcineurin inhibitor-induced nephrotoxicity, as well as in development of renal failure. |
| 1099 | 20099993 | A number of genes are implicated in contributing to diabetes, and these include the vitamin D receptor gene, VDR; hepatocyte nuclear factor genes, HNF; transcription factor 7-like 2 gene, TCF7L2; angiotensin-converting enzyme gene, ACE; cytokines; peroxisome proliferator-activated receptor gamma gene, PPARG; and others. |
| 1100 | 20099993 | Studies have suggested that the VDR, PPARG, HNF1A, and adenosine 5'-triphosphate-binding cassette ABCC8 (which encodes the sulfonylurea receptor) genes are associated with calcineurin inhibitor-induced diabetes. |
| 1101 | 20099993 | The genes encoding for the angiotensin-converting enzyme, endothelial constitutive nitric oxide synthase, and cytochrome P450 3A isoenzyme have been involved in the development of hypertension and in calcineurin inhibitor-induced hypertension. |
| 1102 | 20520596 | In contrast, equally obese, hyperglycemic Lepr/Sur1 deficient C57BL/6J (Sur1 has defective insulin secretion) mice have minimal evidence of nephropathy. |
| 1103 | 20878272 | In this review we describe the progress that has been made to date in translating association signals into molecular mechanisms with a focus on the most tractable signals (eg, KCNJ11/ABCC8, SLC30A8, GCKR) and those in which human, animal, and cellular models (FTO, TCF7L2, G6PC2) have provided insights into the role in T2D pathogenesis. |
| 1104 | 20878482 | The β-cell K(ATP) channel is a hetero-octameric complex composed of two types of subunits: four inward-rectifying potassium channel pore-forming (Kir6.2) subunits and four high-affinity sulfonylurea receptor 1 (SUR1) subunits. |
| 1105 | 20878482 | Kir6.2 and SUR1 are encoded by the genes KCNJ11 and ABCC8, respectively. |
| 1106 | 20878482 | The β-cell K(ATP) channel is a hetero-octameric complex composed of two types of subunits: four inward-rectifying potassium channel pore-forming (Kir6.2) subunits and four high-affinity sulfonylurea receptor 1 (SUR1) subunits. |
| 1107 | 20878482 | Kir6.2 and SUR1 are encoded by the genes KCNJ11 and ABCC8, respectively. |
| 1108 | 20922570 | Permanent neonatal diabetes due to activating mutations in ABCC8 and KCNJ11. |
| 1109 | 20922570 | The ATP-sensitive potassium (K(ATP)) channel is composed of two subunits SUR1 and Kir6.2. |
| 1110 | 20922570 | Activating mutations have been identified in the genes encoding these subunits, ABCC8 and KCNJ11, and account for approximately 40% of permanent neonatal diabetes cases. |
| 1111 | 20922570 | Permanent neonatal diabetes due to activating mutations in ABCC8 and KCNJ11. |
| 1112 | 20922570 | The ATP-sensitive potassium (K(ATP)) channel is composed of two subunits SUR1 and Kir6.2. |
| 1113 | 20922570 | Activating mutations have been identified in the genes encoding these subunits, ABCC8 and KCNJ11, and account for approximately 40% of permanent neonatal diabetes cases. |
| 1114 | 20922570 | Permanent neonatal diabetes due to activating mutations in ABCC8 and KCNJ11. |
| 1115 | 20922570 | The ATP-sensitive potassium (K(ATP)) channel is composed of two subunits SUR1 and Kir6.2. |
| 1116 | 20922570 | Activating mutations have been identified in the genes encoding these subunits, ABCC8 and KCNJ11, and account for approximately 40% of permanent neonatal diabetes cases. |
| 1117 | 20938745 | This is especially true for patients with mutations in the genes KCNJ11 or ABCC8 that encode the two protein subunits (Kir6.2 and SUR1, respectively) of the ATP-sensitive potassium channel. |
| 1118 | 21169132 | Three common variants (Lys23 of KCNJ11, Pro12 of PPARG, and the T allele at rs7903146 of TCF7L2) have been shown to be predisposed to type 2 diabetes mellitus across many large studies. |
| 1119 | 21169132 | Other classes are also mentioned in literature.In this work, different types of genetic mutations (mutations of the gene for glucokinase, HNF 1α, HNF1β and Kir6.2 and SUR1 subunit of KATP channel, PPAR-γ, OCT1 and OCT2, cytochromes, direct drug-receptor (KCNJ11), as well as the factors that influence the development of the disease (TCF7L2) and variants of genes that lead to hepatosteatosis caused by thiazolidinediones) and their influence on the response to therapy with oral antidiabetics will be reviewed. |
| 1120 | 21463240 | Mutations in the GCK gene cause a mild form of diabetes, which seldom needs insulin and has a low risk for complications. |
| 1121 | 21463240 | The majority of neonatal diabetes cases are caused by mutations in the K(ATP) channel genes ABCC8 and KCNJ11, and sulfonylurea therapy is then usually superior to insulin. |
| 1122 | 21515691 | Western blot, RT-PCR, and immunohistochemistry showed expression of the major genes involved in proinsulin processing and the pancreatic beta cell stimulus-secretion pathway including PC1/3, PC2, GLUT-1, glucokinase, and K-ATP channel complex (Sur1 and Kir6.2) and the voltage-dependent L-type Ca(2+) channel. |
| 1123 | 21540348 | A conserved tryptophan at the membrane-water interface acts as a gatekeeper for Kir6.2/SUR1 channels and causes neonatal diabetes when mutated. |
| 1124 | 21540348 | Replacement with tyrosine (Y) rendered the KATP channel almost completely insensitive to ATP block, dramatically increased the channel open probability, and affected the interaction of Kir6.2 with SUR1. |
| 1125 | 21540348 | A conserved tryptophan at the membrane-water interface acts as a gatekeeper for Kir6.2/SUR1 channels and causes neonatal diabetes when mutated. |
| 1126 | 21540348 | Replacement with tyrosine (Y) rendered the KATP channel almost completely insensitive to ATP block, dramatically increased the channel open probability, and affected the interaction of Kir6.2 with SUR1. |
| 1127 | 21671119 | In COS-7 cells triple transfected with SUR1Δ2/SUR1/Kir6.2, the SUR1Δ2 peptide co-immunoprecipitated with Kir6.2, thereby displacing two of four SUR1 subunits on the cell surface. |
| 1128 | 21671119 | A non-mutagenic SNP on nucleotide position 333 (Pro69Pro) added another exonic splicing enhancer sequence detected by ASF/SF2, reduced relative abundance of SUR1Δ2 and slightly protected from non-insulin dependent diabetes in homozygotic individuals. |
| 1129 | 21674179 | Hyperinsulinaemic hypoglycaemia and diabetes mellitus due to dominant ABCC8/KCNJ11 mutations. |
| 1130 | 21796147 | Recently, permanent neonatal diabetes resulting from mutations in the two protein subunits of the adenosine triphosphate-sensitive potassium channel (Kir6.2 and SUR1) has proven to be successfully treatable with high doses of sulfonylureas rather than insulin. |
| 1131 | 21812222 | Understanding of physiopathology increased this last decade, as many mutations in genes playing critical roles in the development of pancreas, have been described: the most common are chromosome 6q anomalies in the case of TND, and mutations in KCNJ11 and ABCC8 genes encoding the subunit of the insulin cell potassium channel in the case of PND. |
| 1132 | 21814221 | We genotyped 91 polymorphisms in 19 genes (ABCC8, HNF1A, HNF1B, HNF4A, INS, INSM1, ISL1, KCNJ11, MAFA, MNX1, NEUROD1, NEUROG3, NKX2.2, NKX6.1, PAX4, PAX6, PDX1, USF1 and WFS1) in 2025 unrelated North Indians of Indo-European ethnicity comprising of 1019 diabetic and 1006 non-diabetic subjects. |
| 1133 | 21814221 | Variants in USF1, ABCC8, ISL1 and KCNJ11 showed nominal association, while haplotypes in these genes were significantly associated. rs3812704 upstream of NEUROG3 significantly increased risk for type 2 diabetes in normal-weight/lean subjects (OR=1.68 (95%CI 1.25-2.24), P=4.9 × 10(-4)). |
| 1134 | 21814221 | We genotyped 91 polymorphisms in 19 genes (ABCC8, HNF1A, HNF1B, HNF4A, INS, INSM1, ISL1, KCNJ11, MAFA, MNX1, NEUROD1, NEUROG3, NKX2.2, NKX6.1, PAX4, PAX6, PDX1, USF1 and WFS1) in 2025 unrelated North Indians of Indo-European ethnicity comprising of 1019 diabetic and 1006 non-diabetic subjects. |
| 1135 | 21814221 | Variants in USF1, ABCC8, ISL1 and KCNJ11 showed nominal association, while haplotypes in these genes were significantly associated. rs3812704 upstream of NEUROG3 significantly increased risk for type 2 diabetes in normal-weight/lean subjects (OR=1.68 (95%CI 1.25-2.24), P=4.9 × 10(-4)). |
| 1136 | 21823539 | Mutations in KCNJ11, ABCC8, or INS are the cause of permanent neonatal diabetes mellitus in about 50%-60% of the patients. |
| 1137 | 21863614 | Genes KCNJ11 and ABCC8 encode potassium channel proteins. |
| 1138 | 21863614 | KCNJ11 gene Glu23Lys polymorphism was associated with an increased risk of SU secondary failure, while Ser1369Ala polymorphism of ABCC8 gene had influence antidiabetic efficacy of SU drug gliclazide. |
| 1139 | 21863614 | Genes KCNJ11 and ABCC8 encode potassium channel proteins. |
| 1140 | 21863614 | KCNJ11 gene Glu23Lys polymorphism was associated with an increased risk of SU secondary failure, while Ser1369Ala polymorphism of ABCC8 gene had influence antidiabetic efficacy of SU drug gliclazide. |
| 1141 | 21953423 | Patients referred to the Italian reference laboratory for NDM between years 2005 and 2010 and screened for mutations in common NDM genes (KCNJ11, ABCC8, and INS) and for uniparental isodisomy of chromosome 6 (UDP6) were reviewed. |
| 1142 | 21953423 | In this group, a mutation of either KCNJ11, ABCC8 or INS was found in 18 patients, and a case with UDP6 was identified. |
| 1143 | 21953423 | Patients referred to the Italian reference laboratory for NDM between years 2005 and 2010 and screened for mutations in common NDM genes (KCNJ11, ABCC8, and INS) and for uniparental isodisomy of chromosome 6 (UDP6) were reviewed. |
| 1144 | 21953423 | In this group, a mutation of either KCNJ11, ABCC8 or INS was found in 18 patients, and a case with UDP6 was identified. |
| 1145 | 21959939 | Some of these gene polymorphisms were identified in the genes encoding the KATP channel (KCNJ11 and ABCC8). |
| 1146 | 21993633 | The most common causes accounting for the majority of cases are mutations in the genes encoding the two subunits of the ATP-sensitive potassium channel (K(ATP)), KCNJ11 and ABCC8, and the insulin gene (INS), as well as abnormalities in chromosome 6q24. |
| 1147 | 21993633 | Patients with activating mutations in KCNJ11 and ABCC8 can be treated with oral sulfonylureas in lieu of insulin injections. |
| 1148 | 21993633 | The most common causes accounting for the majority of cases are mutations in the genes encoding the two subunits of the ATP-sensitive potassium channel (K(ATP)), KCNJ11 and ABCC8, and the insulin gene (INS), as well as abnormalities in chromosome 6q24. |
| 1149 | 21993633 | Patients with activating mutations in KCNJ11 and ABCC8 can be treated with oral sulfonylureas in lieu of insulin injections. |
| 1150 | 22020219 | Here we show that a diabetogenic mutation in an unexplored helix preceding the ABC core of SUR1 dramatically increases open probability of (SUR1/Kir6.2)(4) channel (KATP) by reciprocally changing rates of its transitions to and from the long-lived, inhibitory ligand-stabilized closed state. |
| 1151 | 22020219 | This kinetic mechanism attenuates ATP and sulfonylurea inhibition, but not Mg-nucleotide stimulation, of SUR1/Kir6.2. |
| 1152 | 22020219 | Here we show that a diabetogenic mutation in an unexplored helix preceding the ABC core of SUR1 dramatically increases open probability of (SUR1/Kir6.2)(4) channel (KATP) by reciprocally changing rates of its transitions to and from the long-lived, inhibitory ligand-stabilized closed state. |
| 1153 | 22020219 | This kinetic mechanism attenuates ATP and sulfonylurea inhibition, but not Mg-nucleotide stimulation, of SUR1/Kir6.2. |
| 1154 | 22118586 | Giving insights to beta cell function, CHI mutations are now known in eight genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2). |
| 1155 | 22118705 | It is well known that sulphonylureas (SUs), commonly used in the treatment of type 2 diabetes mellitus, stimulate insulin secretion by closing ATP-sensitive K(+) (K(ATP) ) channels in pancreatic β-cells by binding to the SU receptor SUR1. |
| 1156 | 22118705 | SUs are now known also to activate cAMP sensor Epac2 (cAMP-GEFII) to Rap1 signalling, which promotes insulin granule exocytosis. |
| 1157 | 22118705 | For SUs to exert their full effects in insulin secretion, they are required to activate Epac2 as well as to inhibit the β-cell K(ATP) channels. |
| 1158 | 22118705 | As Epac2 is also necessary for potentiation of glucose-induced insulin secretion by cAMP-increasing agents, such as incretin, Epac2 is a target of both cAMP and SUs. |
| 1159 | 22118705 | The distinct effects of various SUs appear to be because of their different actions on Epac2/Rap1 signalling as well as K(ATP) channels. |
| 1160 | 22231386 | The molecular basis of HH involves defects in key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2) which regulate insulin secretion. |
| 1161 | 22231386 | The most severe forms of HH are due to loss of function mutations in ABCC8/KCNJ11 which encode the SUR1 and KIR6.2 components respectively of the pancreatic β-cell K(ATP) channel. |
| 1162 | 22231386 | The molecular basis of HH involves defects in key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2) which regulate insulin secretion. |
| 1163 | 22231386 | The most severe forms of HH are due to loss of function mutations in ABCC8/KCNJ11 which encode the SUR1 and KIR6.2 components respectively of the pancreatic β-cell K(ATP) channel. |
| 1164 | 22451668 | K(ATP) channels, (SUR1/Kir6.2)(4) (sulfonylurea receptor type 1/potassium inward rectifier type 6.2) respond to the metabolic state of pancreatic β-cells, modulating membrane potential and insulin exocytosis. |
| 1165 | 22451668 | K(ATP) channels are inhibited by ATP binding to the Kir6.2 pore and stimulated, via an uncertain mechanism, by magnesium nucleotides at SUR1. |
| 1166 | 22451668 | K(ATP) channels, (SUR1/Kir6.2)(4) (sulfonylurea receptor type 1/potassium inward rectifier type 6.2) respond to the metabolic state of pancreatic β-cells, modulating membrane potential and insulin exocytosis. |
| 1167 | 22451668 | K(ATP) channels are inhibited by ATP binding to the Kir6.2 pore and stimulated, via an uncertain mechanism, by magnesium nucleotides at SUR1. |
| 1168 | 22492528 | Bile acids acutely stimulate insulin secretion of mouse β-cells via farnesoid X receptor activation and K(ATP) channel inhibition. |
| 1169 | 22492528 | Experiments were performed with islets from wild-type, farnesoid X receptor (FXR) knockout (KO), and β-cell ATP-dependent K(+) (K(ATP)) channel gene SUR1 (ABCC8) KO mice, respectively. |
| 1170 | 22492528 | Sodium ursodeoxycholate, which has a much lower affinity to FXR than TCDC, had no effect on [Ca(2+)](c) and insulin secretion. |
| 1171 | 22509362 | Deregulation of CREB signaling pathway induced by chronic hyperglycemia downregulates NeuroD transcription. |
| 1172 | 22509362 | CREB mediates the transcriptional effects of glucose and incretin hormones in insulin-target cells and insulin-producing β-cells. |
| 1173 | 22509362 | Here, we show that β-cell dysfunctions occurring in chronic hyperglycemia are not caused by simple inhibition of CREB activity but rather by the persistent activation of CREB due to decreases in protein phophatase PP2A. |
| 1174 | 22509362 | The excessively produced ICER was sufficient to repress the transcription of NeuroD, insulin, and SUR1 genes. |
| 1175 | 22509362 | Importantly, overexpression of PP2A reversed the adverse effects of chronic hyperglycemia and successfully restored the transient activation of CREB and ICER. |
| 1176 | 22509362 | Conversely, depletion of PP2A with siRNA was sufficient to disrupt the negative feedback regulation of CREB and induce hyperglycemic phenotypes even under low glucose conditions. |
| 1177 | 22509362 | Our findings suggest that the failure of the negative feedback regulation of CREB is the primary cause for β-cell dysfunctions under conditions of pathogenic hyperglycemia, and PP2A can be a novel target for future therapies aiming to protect β-cells mass in the late transitional phase of non-insulin dependent type 2 diabetes (NIDDM). |
| 1178 | 22796691 | Most cases of permanent form of neonatal diabetes mellitus (PNDM) are due to dominant heterozygous gain of function (activating) mutations in either KCNJ11 or ABCC8 genes, that code for Kir 6.2 and SUR1 subunits, respectively of the pancreatic b cell KATP channel. |
| 1179 | 22815030 | The majority of neonatal DM cases are caused by a heterozygous activating mutation in the KCNJ11 or ABCC8 genes that encode the Kir6.2 and SUR1 protein subunits, respectively, in the KATP channel. |
| 1180 | 22815030 | For patients with KCNJ11 and ABCC8 gene mutation, oral sulphonylurea should be considered. |
| 1181 | 22815030 | The majority of neonatal DM cases are caused by a heterozygous activating mutation in the KCNJ11 or ABCC8 genes that encode the Kir6.2 and SUR1 protein subunits, respectively, in the KATP channel. |
| 1182 | 22815030 | For patients with KCNJ11 and ABCC8 gene mutation, oral sulphonylurea should be considered. |
| 1183 | 22842804 | There have been several reports of the successful transition from insulin to sulfonylurea agents in patients with permanent diabetes mellitus caused by mutations in the KCNJ11 gene. |
| 1184 | 22842804 | We report on a term female neonate with a novel missense mutation, p.P1199L, in the ABCC8 gene that encodes the sulfonylurea receptor 1 whose treatment was successfully converted from insulin to sulfonylurea. |
| 1185 | 22855730 | In preclinical studies, we showed that the GLP-1 receptor antagonist exendin-(9-39) suppresses insulin secretion and corrects fasting hypoglycemia in SUR-1(-/-) mice. |
| 1186 | 22855730 | The primary outcome was blood glucose; secondary outcomes were insulin, glucagon, and GLP-1. |
| 1187 | 22994227 | Here, we provide a focused review on the involvement of matrix metalloproteinase 9 (MMP-9) in rt-PA-associated HT in cerebral ischemia, and we review emerging evidence that the selective inhibitor of the sulfonylurea receptor 1 (Sur1), glibenclamide (U.S. adopted name, glyburide), may provide protection against rt-PA-associated HT in cerebral ischemia. |
| 1188 | 23093687 | Incretin effect of glucagon-like peptide 1 receptor agonist is preserved in presence of ABCC8/SUR1 mutation in β-cell. |
| 1189 | 23226049 | Mutations in the KCNJ11 and ABCC8 genes, encoding the adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel Kir6.2 and SUR1 subunits, respectively, are found in ∼50% of NDM patients. |
| 1190 | 23226049 | In the pancreatic β-cell, K(ATP) channel activity couples glucose metabolism to insulin secretion via cellular excitability and mutations in either KCNJ11 or ABCC8 genes alter K(ATP) channel activity, leading to faulty insulin secretion. |
| 1191 | 23226049 | Many NDM patients with KCNJ11 and ABCC8 mutations can be successfully treated with sulfonylureas (SUs) that inhibit the K(ATP) channel, thus replacing the need for daily insulin injections. |
| 1192 | 23226049 | Mutations in the KCNJ11 and ABCC8 genes, encoding the adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel Kir6.2 and SUR1 subunits, respectively, are found in ∼50% of NDM patients. |
| 1193 | 23226049 | In the pancreatic β-cell, K(ATP) channel activity couples glucose metabolism to insulin secretion via cellular excitability and mutations in either KCNJ11 or ABCC8 genes alter K(ATP) channel activity, leading to faulty insulin secretion. |
| 1194 | 23226049 | Many NDM patients with KCNJ11 and ABCC8 mutations can be successfully treated with sulfonylureas (SUs) that inhibit the K(ATP) channel, thus replacing the need for daily insulin injections. |
| 1195 | 23226049 | Mutations in the KCNJ11 and ABCC8 genes, encoding the adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel Kir6.2 and SUR1 subunits, respectively, are found in ∼50% of NDM patients. |
| 1196 | 23226049 | In the pancreatic β-cell, K(ATP) channel activity couples glucose metabolism to insulin secretion via cellular excitability and mutations in either KCNJ11 or ABCC8 genes alter K(ATP) channel activity, leading to faulty insulin secretion. |
| 1197 | 23226049 | Many NDM patients with KCNJ11 and ABCC8 mutations can be successfully treated with sulfonylureas (SUs) that inhibit the K(ATP) channel, thus replacing the need for daily insulin injections. |
| 1198 | 23341697 | Maternal protein restriction induces alterations in insulin signaling and ATP sensitive potassium channel protein in hypothalami of intrauterine growth restriction fetal rats. |
| 1199 | 23341697 | There was also a downregulation of the hypothalamic ATP sensitive potassium channel subunit, sulfonylurea receptor 1, which conveys the insulin signaling. |
| 1200 | 23639568 | Permanent neonatal diabetes mellitus is a rare condition mostly due to heterozygous mutations in the KCNJ11, ABCC8 and INS genes. |
| 1201 | 23639568 | Mutations in PDX1, PTF1A, HNF1B, EIF2AK3, RFX6 and GATA6 genes have been shown to result in pancreatic agenesis or hypoplasia. |
| 1202 | 23665564 | Neuroendocrine-type K(ATP) channels, (SUR1/Kir6.2)4, couple the transmembrane flux of K(+), and thus membrane potential, with cellular metabolism in various cell types including insulin-secreting β-cells. |
| 1203 | 23665564 | A current regulatory model proposes that ATP hydrolysis is required to switch SUR1 into post-hydrolytic conformations able to antagonize the inhibitory action of nucleotide binding at the Kir6.2 pore, thus coupling enzymatic and channel activities. |
| 1204 | 23665564 | Neuroendocrine-type K(ATP) channels, (SUR1/Kir6.2)4, couple the transmembrane flux of K(+), and thus membrane potential, with cellular metabolism in various cell types including insulin-secreting β-cells. |
| 1205 | 23665564 | A current regulatory model proposes that ATP hydrolysis is required to switch SUR1 into post-hydrolytic conformations able to antagonize the inhibitory action of nucleotide binding at the Kir6.2 pore, thus coupling enzymatic and channel activities. |
| 1206 | 23667671 | Gain of channel function (GOF) mutations in the genes encoding Kir6.2 (KCNJ11) or the associated regulatory ssulfonylurea receptor 1 subunit (ABCC8), cause developmental delay, epilepsy and neonatal diabetes (DEND) due to suppressed cell excitability in pancreatic β-cells and neurons. |
| 1207 | 23667671 | The naturally occurring Kir6.2 mutation plus deletion (Ser225Thr, Pro226_Pro232del) as well as the isolated S225T mutation or isolated del226-232 deletion were coexpressed with SUR1 in COS cells in homozygous or heterozygous states. |
| 1208 | 23667671 | Gain of channel function (GOF) mutations in the genes encoding Kir6.2 (KCNJ11) or the associated regulatory ssulfonylurea receptor 1 subunit (ABCC8), cause developmental delay, epilepsy and neonatal diabetes (DEND) due to suppressed cell excitability in pancreatic β-cells and neurons. |
| 1209 | 23667671 | The naturally occurring Kir6.2 mutation plus deletion (Ser225Thr, Pro226_Pro232del) as well as the isolated S225T mutation or isolated del226-232 deletion were coexpressed with SUR1 in COS cells in homozygous or heterozygous states. |
| 1210 | 23736775 | A Short-activating RNA Oligonucleotide Targeting the Islet β-cell Transcriptional Factor MafA in CD34(+) Cells. |
| 1211 | 23736775 | We have developed a novel approach using short-activating RNA oligonucleotides to differentiate adult human CD34(+) cells into insulin-secreting cells. |
| 1212 | 23736775 | By transfecting RNA to increase transcript levels of the master regulator of insulin biosynthesis, v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), several pancreatic endodermal genes were upregulated during the differentiation procedure. |
| 1213 | 23736775 | These included Pancreatic and duodenal homeobox gene-1 (PDX1), Neurogenin 3, NeuroD, and NK6 homeobox 1 (NKx6-1). |
| 1214 | 23736775 | Differentiated CD34(+) cells also expressed glucokinase, glucagon-like peptide 1 receptor (GLP1R), sulfonylurea receptor-1 (SUR1) and phogrin-all essential for glucose sensitivity and insulin secretion. |
| 1215 | 23764562 | Association of adiponectin (AdipoQ) and sulphonylurea receptor (ABCC8) gene polymorphisms with Type 2 Diabetes in North Indian population of Punjab. |
| 1216 | 23764562 | In Type 2 Diabetes (T2D), adiponectin (AdipoQ) and sulphonylurea receptor genes (ABCC8) are important targets for candidate gene association studies. |
| 1217 | 23764562 | The present case-control study undertaken in the population of Punjab, evaluates the association of +45T>G polymorphism in AdipoQ gene; and Exon16-3C>T as well as Exon18C>T polymorphisms in ABCC8 gene with T2D. |
| 1218 | 23764562 | Association of adiponectin (AdipoQ) and sulphonylurea receptor (ABCC8) gene polymorphisms with Type 2 Diabetes in North Indian population of Punjab. |
| 1219 | 23764562 | In Type 2 Diabetes (T2D), adiponectin (AdipoQ) and sulphonylurea receptor genes (ABCC8) are important targets for candidate gene association studies. |
| 1220 | 23764562 | The present case-control study undertaken in the population of Punjab, evaluates the association of +45T>G polymorphism in AdipoQ gene; and Exon16-3C>T as well as Exon18C>T polymorphisms in ABCC8 gene with T2D. |
| 1221 | 23764562 | Association of adiponectin (AdipoQ) and sulphonylurea receptor (ABCC8) gene polymorphisms with Type 2 Diabetes in North Indian population of Punjab. |
| 1222 | 23764562 | In Type 2 Diabetes (T2D), adiponectin (AdipoQ) and sulphonylurea receptor genes (ABCC8) are important targets for candidate gene association studies. |
| 1223 | 23764562 | The present case-control study undertaken in the population of Punjab, evaluates the association of +45T>G polymorphism in AdipoQ gene; and Exon16-3C>T as well as Exon18C>T polymorphisms in ABCC8 gene with T2D. |
| 1224 | 23828045 | At 1 week after multiple low-dose STZ administrations, pancreatic β-cells showed impaired insulin expression, while maintaining expression of nuclear Nkx6.1. |
| 1225 | 23828045 | This was accompanied by significant upregulation of p53-responsive genes in islets, including a mediator of cell cycle arrest, p21 (also known as Waf1 and Cip1). |
| 1226 | 23828045 | STZ treatment also suppressed expression of a wide range of genes linked with key β-cell functions or diabetes development, such as G6pc2, Slc2a2 (Glut2), Slc30a8, Neurod1, Ucn3, Gad1, Isl1, Foxa2, Vdr, Pdx1, Fkbp1b and Abcc8, suggesting global β-cell defects in STZ-treated islets. |
| 1227 | 23828045 | When a pancreas-targeted adeno-associated virus (AAV) vector was employed for long-term Glp-1 gene delivery, pancreatic GLP-1 expression protected mice from STZ-induced diabetes through preservation of the β-cell mass. |
| 1228 | 23828045 | Upon pancreatic GLP-1 expression, upregulation of Cxcl13 and Nptx2 was observed in STZ-damaged islets, but not in untreated normal islets. |
| 1229 | 23828045 | Given the pro-β-cell-survival effects of Cxcl12 (Sdf-1) in inducing GLP-1 production in α-cells, pancreatic GLP-1-mediated Cxcl13 induction might also play a crucial role in maintaining the integrity of β-cells in damaged islets. |
| 1230 | 23903354 | Loss-of-function mutations in the KATP channel genes KCNJ11 and ABCC8 cause neonatal hyperinsulinism in humans. |
| 1231 | 23926410 | ABCC8 encodes the sulfonylurea receptor 1 (SUR1) subunits of the beta-cell ATP-sensitive potassium (K-ATP) channel playing a critical role in the regulation of insulin secretion, and inactivating mutations in ABCC8 cause congenital hyperinsulinism. |
| 1232 | 23926410 | Hypoglycemia was improved by the combination of nateglinide, which stimulates early insulin secretion, and an alpha-glucosidase inhibitor, voglibose. |
| 1233 | 23926410 | Sequencing of the ABCC8 identified a compound heterozygous mutation (R1420H/F591fs604X), suggesting that this mutation may alter regulation of insulin secretion with advancing age, leading to diabetes mellitus with reactive hypoglycemia from hyperinsulinism. |
| 1234 | 23926410 | Therefore, long-term follow-up and periodic OGTTs are important for early detection of insulin dysregulation in congenital hyperinsulinism patients carrying the ABCC8 mutation, even though hypoglycemia resolves spontaneously during infancy. |
| 1235 | 23926410 | ABCC8 encodes the sulfonylurea receptor 1 (SUR1) subunits of the beta-cell ATP-sensitive potassium (K-ATP) channel playing a critical role in the regulation of insulin secretion, and inactivating mutations in ABCC8 cause congenital hyperinsulinism. |
| 1236 | 23926410 | Hypoglycemia was improved by the combination of nateglinide, which stimulates early insulin secretion, and an alpha-glucosidase inhibitor, voglibose. |
| 1237 | 23926410 | Sequencing of the ABCC8 identified a compound heterozygous mutation (R1420H/F591fs604X), suggesting that this mutation may alter regulation of insulin secretion with advancing age, leading to diabetes mellitus with reactive hypoglycemia from hyperinsulinism. |
| 1238 | 23926410 | Therefore, long-term follow-up and periodic OGTTs are important for early detection of insulin dysregulation in congenital hyperinsulinism patients carrying the ABCC8 mutation, even though hypoglycemia resolves spontaneously during infancy. |
| 1239 | 23926410 | ABCC8 encodes the sulfonylurea receptor 1 (SUR1) subunits of the beta-cell ATP-sensitive potassium (K-ATP) channel playing a critical role in the regulation of insulin secretion, and inactivating mutations in ABCC8 cause congenital hyperinsulinism. |
| 1240 | 23926410 | Hypoglycemia was improved by the combination of nateglinide, which stimulates early insulin secretion, and an alpha-glucosidase inhibitor, voglibose. |
| 1241 | 23926410 | Sequencing of the ABCC8 identified a compound heterozygous mutation (R1420H/F591fs604X), suggesting that this mutation may alter regulation of insulin secretion with advancing age, leading to diabetes mellitus with reactive hypoglycemia from hyperinsulinism. |
| 1242 | 23926410 | Therefore, long-term follow-up and periodic OGTTs are important for early detection of insulin dysregulation in congenital hyperinsulinism patients carrying the ABCC8 mutation, even though hypoglycemia resolves spontaneously during infancy. |
| 1243 | 23985558 | Exposure to 25 mM glucose significantly reduced insulin content (p<0.05) and glucokinase activity (p<0.01) after 72 h. |
| 1244 | 23985558 | Effects of hyperglycemia on secretory function were accompanied by decreased mRNA expression of INS, GCK, PCSK1, PCSK2, PPP3CB, GJA1, ABCC8, and KCNJ11. |
| 1245 | 23985558 | Hyperglycemia-induced apoptosis was evident from increased activity of caspase 3/7 and decreased BCL2 protein. |
| 1246 | 17082235 | Most drugs currently employed in the treatment of type 2 diabetes either target the sulfonylurea receptor stimulating insulin release (sulfonylureas, glinides), or target the peroxisome proliferator-activated receptor (PPARgamma) improving insulin resistance (thiazolidinediones). |
| 1247 | 17082235 | This dual mode of action of sulfonylureas and glinides may open new perspectives for the molecular pharmacology of antidiabetic drugs, because it provides evidence that drugs can be designed that target both the sulfonylurea receptor and PPARgamma. |
| 1248 | 17082235 | Most drugs currently employed in the treatment of type 2 diabetes either target the sulfonylurea receptor stimulating insulin release (sulfonylureas, glinides), or target the peroxisome proliferator-activated receptor (PPARgamma) improving insulin resistance (thiazolidinediones). |
| 1249 | 17082235 | This dual mode of action of sulfonylureas and glinides may open new perspectives for the molecular pharmacology of antidiabetic drugs, because it provides evidence that drugs can be designed that target both the sulfonylurea receptor and PPARgamma. |