title: Possible contributions of lipoproteins and cholesterol to the pathogenesis of diabetes mellitus type 2.
abstract: OBJECTIVE
  Low HDL cholesterol and hypertriglyceridemia as well as lowering of LDL cholesterol with statins increase the risk of T2DM. We discuss the recent findings on the effects of lipoproteins and cholesterol on the function and survival of pancreatic β-cells as well as on obesity and insulin sensitivity of muscle and liver.
  
  
  RESULTS
  LDL inhibits glucose-stimulated insulin secretion and proliferation of β-cells by LDL-receptor dependent and independent mechanisms, respectively. ApoA-I and HDL stimulate insulin secretion by interaction with ABCA1, ABCG1 or SR-BI and also inhibit apoptosis of β-cells. Mice with targeted knockouts of ABCA1 or ABCG1 in β-cells show reduced insulin secretion and glucose tolerance. ABCG1 contributes to the enrichment of insulin secretory granules with cholesterol, which is needed for their formation and trafficking to the plasma membrane whereas ABCA1-mediated cholesterol efflux from the plasma membrane appears to be important for their subsequent exocytosis. In mice, overexpression of apoA-I decreases body fat accumulation and increases insulin sensitivity of muscle and liver by inducing the phosphorylation of AMP kinase.
  
  
  CONCLUSIONS
  LDL, HDL and cholesterol regulate the function and survival of β-cells. HDL also exerts antiobesity and insulin-sensitizing effects. Thus dyslipidemias may not only be consequences but also contributors to the pathogenesis and hence targets for prevention of T2DM.
authors.affiliation: Institute of Clinical Chemistry, University and University Hospital Zurich, Switzerland. Arnold.voneckardstein@usz.ch
authors.forename: Arnold
authors.initials: A
authors.lastname: von Eckardstein
authors.forename: Rahel A
authors.initials: RA
authors.lastname: Sibler
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism*
chemical_list: D008074:Lipoproteins; D002784:Cholesterol