Insulin contributes to fine-tuning of the pancreatic beta-cell response to glucagon-like peptide-1

Mi Jin Moon, Hee Young Kim, Sumi Park, Dong Kyu Kim, Eun Bee Cho, Jong Ik Hwang, Jae Young Seong

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion from pancreatic ß-cells in a glucose-dependent manner. However, factors other than glucose that regulate the ß-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 ß-cells. Pretreatment of ß-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 ß- 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 ß-cells were exposed to high glucose for 18 h. Treatment of ß-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 ß-cell response to GLP-1.

Original languageEnglish
Pages (from-to)389-395
Number of pages7
JournalMolecules and cells
Volume32
Issue number4
DOIs
Publication statusPublished - 2011 Oct

Keywords

  • CAMP
  • Erk
  • GLP-1
  • Insulin
  • RTK
  • ß-cells

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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