Adiponectin-mediated stimulation of AMP-activated protein kinase (AMPK) in pancreatic beta cells.
The adipocyte-derived hormone adiponectin was recently shown to stimulate glucose-utilization and to increase fatty acid oxidation in liver and muscle. The effects were ascribed to adiponectin-receptor mediated activation of the key metabolic regulator AMP-activated protein kinase (AMPK). In pancreatic beta cells, AMPK-activation is known to affect cellular function. We therefore investigated a possible adiponectin-induced activation of AMPK in beta cells. RT-PCR analysis confirmed the expression of adiponectin receptor subtypes 1 and 2 in rat beta cells and showed their expression in insulin-secreting MIN6 cells. Culture with physiological concentrations (2.5 microg/ml) of globular adiponectin was found to increase the phosphorylation of both AMPK and acetylcoA carboxylase (ACC) in these cell types. Like the pharmacological AMPK activator 5-amino-imidazole-4-carboxamide-riboside (AICAR), adiponectin activated AMPK in beta cells and MIN6 cells. In short-term incubations of MIN6 cells with either adiponectin (2.5 microg/ml) or AICAR (1 mM), the flux of glucose-carbon to acyl CoA/cholesterol biosynthetic intermediates was reduced. We conclude that adiponectin induces an activation of AMPK in beta cells, which inhibits their cataplerosis of glucose-carbon to lipids.
Huypens
Peter
P
Diabetes Research Center, Brussels Free University-VUB, Brussels, Laarbeeklaan 103, B-1090 Brussels, Belgium.
Moens
Karen
K
Heimberg
Harry
H
Ling
Zhidong
Z
Pipeleers
Daniël
D
Van de Casteele
Mark
M
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D052242:Adiponectin; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D007515:Islets of Langerhans / Q000201:enzymology*; D008055:Lipids / Q000096:biosynthesis; D008297:Male; D009097:Multienzyme Complexes / Q000096:biosynthesis*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012265:Ribonucleotides / Q000494:pharmacology
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; C031143:AICA ribonucleotide; D005947:Glucose