5-amino-imidazole carboxamide riboside acutely potentiates glucose-stimulated insulin secretion from mouse pancreatic islets by KATP channel-dependent and -independent pathways.
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.
Wang
Chang-Zheng
CZ
Department of Biochemistry and Molecular Biology, The University of Chicago, IL 60637, USA. cwang1@uchicago.edu
Wang
Yong
Y
Di
Anke
A
Magnuson
Mark A
MA
Ye
Honggang
H
Roe
Michael W
MW
Nelson
Deborah J
DJ
Bell
Graeme I
GI
Philipson
Louis H
LH
D055372:AMP-Activated Protein Kinases; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000255:Adenosine Triphosphate / Q000502:physiology; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009097:Multienzyme Complexes / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011955:Receptors, Drug; D012263:Ribonucleosides / Q000494:pharmacology*; D064233:Sulfonylurea Receptors
D055372:AMP-Activated Protein Kinases; D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate; D000620:Aminoimidazole Carboxamide; D002118:Calcium; D005947:Glucose; D007328:Insulin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009097:Multienzyme Complexes; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D017346:Protein Serine-Threonine Kinases; D011955:Receptors, Drug; D012263:Ribonucleosides; D064233:Sulfonylurea Receptors; C577508:Abcc8 protein, mouse; C011651:acadesine