Adiponectin increases insulin content and cell proliferation in MIN6 cells via PPARγ-dependent and PPARγ-independent mechanisms

Aims Adiponectin is an important adipokine whose levels are decreased in obesity despite increases in adipocyte mass. Studies in animal models implicate adiponectin as an insulin sensitizer in skeletal muscle and liver. Thiazolidinediones (TZDs) are insulin sensitizers and ligands for peroxisome proliferator-activated ? receptors (PPAR gamma) and these receptors are expressed in beta cells where their activation promotes cell survival. We hypothesize that adiponectin promotes beta cell survival by activating PPAR gamma. Methods We used MIN6 cells to investigate the effect of adiponectin on PPAR gamma expression, beta-cell proliferation, insulin synthesis and insulin secretion. Results We demonstrate that MIN6 cells contain adiponectin receptors and that adiponectin activates PPAR gamma mRNA and protein expression. This increase in PPAR gamma expression is blocked by the PPAR gamma antagonist, GW9662, indicating a transcriptional feedback loop involving PPAR gamma activation of itself. Adiponectin causes a significant increase in insulin content and secretion and this occurs also via PPAR gamma activation due to the inhibitory effect of GW9662. Adiponectin also promotes MIN6 cell proliferation, however, this effect is independent of PPAR gamma activation. Conclusions Our results identify novel roles for the adipokine, adiponectin, in beta-cells function. Adiponectin upregulates PPAR gamma expression, insulin content and insulin secretion through PPAR gamma-dependent mechanisms. Reductions in circulating adiponectin levels in obese individuals could therefore result in negative effects on beta-cell function and this may have direct relevance to beta-cell dysfunction in type 2 diabetes.