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Regulation of glucose-dependent insulin secretion by insulin: Possible role of AMP-activated protein kinase
- Source :
-
Life Sciences . Jul2009, Vol. 85 Issue 3/4, p178-183. 6p. - Publication Year :
- 2009
-
Abstract
- Abstract: Aims: Extracellular insulin affects insulin secretion from pancreatic β-cells in an autocrine fashion, but the role of glucose in this signaling pathway remains unclear. This study was conducted to evaluate the glucose dependency of extracellular insulin-mediated regulation of insulin secretion and the potential underlying mechanism. Main methods: Pancreatic β-cells from male Sprague–Dawley rats and INS-1, a rat insulinoma cell line, were used. The mechanism of extracellular insulin-mediated, glucose-dependent insulin secretion was explored by analyzing the activity of ATP-sensitive K+ (KATP) channels, changes in cell membrane potential, and cytosolic free Ca2+ concentration ([Ca2+]c), as well as phosphorylation of the insulin signaling pathway and the metabolic sensor AMP-activated protein kinase (AMPK). Key findings: Treatment of native β-cells with 100 nM insulin under basal glucose conditions (≤5 mM) reduced subsequent high glucose-induced insulin secretory responses, demonstrating less inhibition of KATP channels and decreased elevation of [Ca2+]c. In contrast, insulin treatment under high glucose conditions potentiated the insulin secretory responses of β-cells. While insulin treatment attenuated phosphorylation on the Thr172 of AMPK and the Ser789 of insulin receptor substrate (IRS)-1, which was increased by lowering glucose concentration, it enhanced phosphorylation of AMPK and IRS-1, which was decreased by elevating glucose concentration. This glucose-dependent regulation of insulin even occurred in the presence of LY294002, a phosphoinositide-3 kinase inhibitor. Significance: Considering that the phosphorylated AMPK could inhibit KATP currents in β-cells, which triggers glucose-stimulated insulin secretion, extracellular insulin may regulate the phosphorylation status of AMPK through IRS-1 to modulate insulin secretion in a glucose-dependent way. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00243205
- Volume :
- 85
- Issue :
- 3/4
- Database :
- Academic Search Index
- Journal :
- Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 42966870
- Full Text :
- https://doi.org/10.1016/j.lfs.2009.05.010