title: Apolipoprotein A-I interactions with insulin secretion and production.
abstract: OBJECTIVE
  Human population studies have established that an elevated plasma high-density lipoprotein cholesterol (HDL-C) level is associated with a decreased risk of developing cardiovascular disease. In addition to having several potentially cardioprotective functions, HDLs and apolipoprotein (apo)A-I, the main HDL apolipoprotein, also have antidiabetic properties. Interventions that elevate plasma HDL-C and apoA-I levels improve glycemic control in people with type 2 diabetes mellitus by enhancing pancreatic β-cell function and increasing insulin sensitivity.
  
  
  RESULTS
  This review is concerned with recent advances in understanding the mechanisms by which HDLs and apoA-I improve pancreatic β-cell function.
  
  
  CONCLUSIONS
  HDLs and apoA-I increase insulin synthesis and secretion in pancreatic β cells. The underlying mechanism of this effect is similar to what has been reported for intestinally derived incretins, such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, which both increase β-cell insulin secretion under high glucose conditions. This involves the activation of a heterotrimeric G protein Gαs subunit on the β-cell surface that leads to induction of a transmembrane adenylyl cyclase, increased intracellular cyclic adenosine monophosphate and Ca levels, and activation of protein kinase A. Protein kinase A increases insulin synthesis by excluding FoxO1 from the β-cell nucleus and derepressing transcription of the insulin gene.
authors.affiliation: School of Medical Sciences, Faculty of Medicine, The University of New South Wales Sydney, New South Wales, Australia.
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.forename: Blake J
authors.initials: BJ
authors.lastname: Cochran
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008075:Lipoproteins, HDL / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D007328:Insulin; D008075:Lipoproteins, HDL; D052216:Glucagon-Like Peptide 1