title: Insulin contributes to fine-tuning of the pancreatic beta-cell response to glucagon-like peptide-1.
abstract: Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion from pancreatic β-cells in a glucose-dependent manner. However, factors other than glucose that regulate the β-cell response to GLP-1 remain poorly understood. In this study, we examined the possible involvement of insulin and receptor tyrosine kinase signaling in regulation of the GLP-1 responsiveness of β-cells. Pretreatment of β-cells with HNMPA, an insulin receptor inhibitor, and AG1478, an epidermal growth factor receptor inhibitor, further increased the cAMP level and Erk phosphorylation in the presence of exendin-4 (exe-4), a GLP-1 agonist. When β-cells were exposed to a high concentration of glucose (25 mM), which stimulates insulin secretion, exe-4-induced cAMP formation declined gradually as exposure time was increased. This decreased cAMP formation was not observed in the presence of HNMPA. HNMPA was able to further increase the exe-4-induced insulin secretion when β-cells were exposed to high glucose for 18 h. Treatment of β-cells with insulin significantly decreased exe-4-induced cAMP formation in a dose-dependent manner. Lowering the phospho-Akt level by HNMPA or LY294002, a PI3K inhibitor, further augmented exe-4-induced cAMP formation and Erk phosphorylation. These results suggest that insulin contributes to fine-tuning of the β-cell response to GLP-1.
authors: Graduate School of Medicine, Korea University, Seoul 136-705, Korea.
authors: Mi Jin
authors: MJ
authors: Moon
authors: Hee Young
authors: HY
authors: Kim
authors: Sumi
authors: S
authors: Park
authors: Dong-Kyu
authors: DK
authors: Kim
authors: Eun Bee
authors: EB
authors: Cho
authors: Jong-Ik
authors: JI
authors: Hwang
authors: Jae Young
authors: JY
authors: Seong
mesh_terms: D000818:Animals; D002460:Cell Line; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D007546:Isoquinolines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D063065:Organophosphonates / Q000494:pharmacology; D010766:Phosphorylation; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D020239:Receptor Cross-Talk; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D013777:Tetrazoles / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D007328:Insulin; D007546:Isoquinolines; D009281:Naphthalenes; D063065:Organophosphonates; D011799:Quinazolines; D018091:Receptors, AMPA; D013777:Tetrazoles; D020032:Tyrphostins; C519736:hydroxy-2-naphthalenyl-methyl phosphonic acid trisacetoxymethylester; C101044:RTKI cpd; C082309:tezampanel; D052216:Glucagon-Like Peptide 1; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt; D005947:Glucose