title: Adiponectin increases insulin content and cell proliferation in MIN6 cells via PPARγ-dependent and PPARγ-independent mechanisms.
abstract: OBJECTIVE
  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 γ receptors (PPARγ) and these receptors are expressed in β cells where their activation promotes cell survival. We hypothesize that adiponectin promotes β cell survival by activating PPARγ.
  
  
  METHODS
  We used MIN6 cells to investigate the effect of adiponectin on PPARγ expression, β-cell proliferation, insulin synthesis and insulin secretion.
  
  
  RESULTS
  We demonstrate that MIN6 cells contain adiponectin receptors and that adiponectin activates PPARγ mRNA and protein expression. This increase in PPARγ expression is blocked by the PPARγ antagonist, GW9662, indicating a transcriptional feedback loop involving PPARγ activation of itself. Adiponectin causes a significant increase in insulin content and secretion and this occurs also via PPARγ activation due to the inhibitory effect of GW9662. Adiponectin also promotes MIN6 cell proliferation, however, this effect is independent of PPARγ activation.
  
  
  CONCLUSIONS
  Our results identify novel roles for the adipokine, adiponectin, in β-cells function. Adiponectin upregulates PPARγ expression, insulin content and insulin secretion through PPARγ-dependent mechanisms. Reductions in circulating adiponectin levels in obese individuals could therefore result in negative effects on β-cell function and this may have direct relevance to β-cell dysfunction in type 2 diabetes.
authors.affiliation: Prince Henry's Institute of Medical Research, Melbourne, Victoria, Australia.
authors.forename: J R
authors.initials: JR
authors.lastname: Rao
authors.forename: D J
authors.initials: DJ
authors.lastname: Keating
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: H C
authors.initials: HC
authors.lastname: Parkington
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D005784:Gene Amplification; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D047495:PPAR gamma / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger; D051381:Rats; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D052242:Adiponectin; D007328:Insulin; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones