Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9884427 | Biochemical and Biophysical Research Communications | 2005 | 7 Pages |
Abstract
AMP-activated protein kinase (AMPK) is an important signaling effector that couples cellular metabolism and function. The effects of AMPK activation on pancreatic β-cell function remain unresolved. We used 5-amino-imidazole carboxamide riboside (AICAR), an activator of AMPK, to define the signaling mechanisms linking the activation of AMPK with insulin secretion. Application of 300 μM AICAR to mouse islets incubated in 5-14 mM glucose significantly increased AMPK activity and potentiated insulin secretion. AICAR inhibited ATP-sensitive K+ (KATP) channels and increased the frequency of glucose-induced calcium oscillations in islets incubated in 8-14 mM glucose. At lower glucose concentration (5 mM) AICAR did not affect KATP activity or intracellular ([Ca2+]i). AICAR also did not inhibit 86Rb+ efflux from islets isolated from Sur1â/â mice that lack KATP channels yet significantly potentiated glucose stimulated insulin secretion. Our data suggest that AICAR stimulates insulin secretion by both KATP channel-dependent and -independent pathways.
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Chang-Zheng Wang, Yong Wang, Anke Di, Mark A. Magnuson, Honggang Ye, Michael W. Roe, Deborah J. Nelson, Graeme I. Bell, Louis H. Philipson,