Insulin Contributes to Fine-Tuning of the Pancreatic Beta-Cell Response to Glucagon-Like Peptide-1

• Published in: Molecules and cells Vol. 32; no. 4; pp. 389 - 396
• Main Authors: Moon, M.J., Korea University, Seoul, Republic of Korea, Kim, H.Y., Korea University College of Medicine, Seoul, Republic of Korea, Park, S.M., Korea University, Seoul, Republic of Korea, Kim, D.K., Korea University, Seoul, Republic of Korea, Cho, E.B., Korea University, Seoul, Republic of Korea, Hwang, J.I., Korea University, Seoul, Republic of Korea, Seong, J.Y., Korea University, Seoul, Republic of Korea
• Format: Journal Article
• Language: English
• Published: Springer Korean Society for Molecular and Cellular Biology 01.10.2011; 한국분자세포생물학회
• Subjects: Animals; beta-cells; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; cAMP; Cell Biology; Cell Line; ErbB Receptors - antagonists & inhibitors; Erk; GLP-1; Glucagon-Like Peptide 1 - metabolism; Glucose - metabolism; INSULIN; Insulin - metabolism; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; INSULINA; INSULINE; Isoquinolines - pharmacology; Life Sciences; Naphthalenes - pharmacology; Oncogene Protein v-akt - metabolism; Organophosphonates - pharmacology; Phosphorylation; Quinazolines - pharmacology; Rats; Receptor Cross-Talk; Receptors, AMPA - antagonists & inhibitors; RTK; Tetrazoles - pharmacology; Tyrphostins - pharmacology; 생물학; RTK; GLP-1; insulin; cAMP; β-cells; Erk
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1007/s10059-011-0157-9

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.