Apolipoprotein A-I interactions with insulin secretion and productionRye, Kerry-Anne; Barter, Philip J.; Cochran, Blake J.Current Opinion in Lipidology: February 2016 - Volume 27 - Issue 1 - p 8–13 doi: 10.1097/MOL.0000000000000253 NUTRITION AND METABOLISM: Edited by Frank M. Sacks and Majken K. Jensen Buy Abstract Author InformationAuthors Article MetricsMetrics Purpose of review 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. Recent findings This review is concerned with recent advances in understanding the mechanisms by which HDLs and apoA-I improve pancreatic β-cell function. Summary 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 Ca2+ 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. School of Medical Sciences, Faculty of Medicine, The University of New South Wales Sydney, New South Wales, Australia Correspondence to Professor Kerry-Anne Rye, School of Medical Sciences, Level 3, Lowy Center, Faculty of Medicine, The University of New South Wales Sydney, NSW 2052, Australia. Tel: +612 9385 1219; fax: +612 9385 1797; e-mail: email@example.com@ozemail.com.au Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.