5-amino-imidazole carboxamide riboside acutely potentiates glucose-stimulated insulin secretion from mouse pancreatic islets by KATP channel-dependent and -independent pathways.

Wang CZ, Wang Y, Di A, Magnuson MA, Ye H, Roe MW, Nelson DJ, Bell GI, Philipson LH
Biochem Biophys Res Commun. 2005 330 (4): 1073-9

PMID: 15823553 · DOI:10.1016/j.bbrc.2005.03.093

AMP-activated protein kinase (AMPK) is an important signaling effector that couples cellular metabolism and function. The effects of AMPK activation on pancreatic beta-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 microM AICAR to mouse islets incubated in 5-14 mM glucose significantly increased AMPK activity and potentiated insulin secretion. AICAR inhibited ATP-sensitive K(+) (K(ATP)) channels and increased the frequency of glucose-induced calcium oscillations in islets incubated in 8-14 mM glucose. At lower glucose concentration (5mM) AICAR did not affect K(ATP) activity or intracellular ([Ca(2+)](i)). AICAR also did not inhibit (86)Rb(+) efflux from islets isolated from Sur1(-/-) mice that lack K(ATP) channels yet significantly potentiated glucose stimulated insulin secretion. Our data suggest that AICAR stimulates insulin secretion by both K(ATP) channel-dependent and -independent pathways.

MeSH Terms (24)

Adenosine Triphosphate Aminoimidazole Carboxamide AMP-Activated Protein Kinases Animals ATP-Binding Cassette Transporters Calcium Drug Synergism Enzyme Activation Glucose Insulin Insulin Secretion In Vitro Techniques Islets of Langerhans Mice Mice, Inbred C57BL Mice, Knockout Multidrug Resistance-Associated Proteins Multienzyme Complexes Potassium Channels Potassium Channels, Inwardly Rectifying Protein-Serine-Threonine Kinases Receptors, Drug Ribonucleosides Sulfonylurea Receptors

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