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

Jyothsna R Rao, Damien J Keating, Chen Chen, Helena C Parkington

Research output: Contribution to journalArticleResearchpeer-review

33 Citations (Scopus)

Abstract

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 gamma receptors (PPARgamma) and these receptors are expressed in beta cells where their activation promotes cell survival. We hypothesize that adiponectin promotes beta cell survival by activating PPARgamma. METHODS: We used MIN6 cells to investigate the effect of adiponectin on PPARgamma expression, beta cell proliferation, insulin synthesis and insulin secretion. RESULTS: We demonstrate that MIN6 cells contain adiponectin receptors and that adiponectin activates PPARgamma mRNA and protein expression. This increase in PPARgamma expression is blocked by the PPARgamma antagonist, GW9662, indicating a transcriptional feedback loop involving PPARgamma activation of itself. Adiponectin causes a significant increase in insulin content and secretion and this occurs also via PPARgamma activation due to the inhibitory effect of GW9662. Adiponectin also promotes MIN6 cell proliferation, however this effect is independent of PPARgamma activation. CONCLUSIONS: Our results identify novel roles of the adipokine, adiponectin, in beta-cells function. Adiponectin upregulates PPARgamma expression, insulin content and insulin secretion through PPARgamma-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.
Original languageEnglish
Pages (from-to)983 - 989
Number of pages7
JournalDiabetes, Obesity and Metabolism
Volume14
Issue number11
DOIs
Publication statusPublished - 2012

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