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Effects of High-Density Lipoproteins on Pancreatic -Cell Insulin Secretion Michelle A. Fryirs, Philip J. Barter, Mathiyalagan Appavoo, Bernard E. Tuch, Fatiha Tabet, Alison K. Heather, Kerry-Anne Rye Objective—Type 2 diabetes is characterized by impaired -cell secretory function, insulin resistance, reduced high-density lipoprotein (HDL) levels, and increased cardiovascular risk. Given the current interest in therapeutic interventions that raise HDLs levels, this study investigates the effects of HDLs on insulin secretion from -cells. Methods and Results—Incubation of Min6 cells and primary islets under basal or high-glucose conditions with either apolipoprotein (apo) A-I or apoA-II in the lipid-free form, as a constituent of discoidal reconstituted HDLs (rHDLs), or with HDLs isolated from human plasma increased insulin secretion up to 5-fold in a calcium-dependent manner. The increase was time and concentration dependent. It was also K channel and glucose metabolism dependent under ATP high-glucose, but not low-glucose, conditions. The lipid-free apolipoprotein-mediated increase in insulin secretion was ATP binding cassette (ABC) transporter A1 and scavenger receptor-B1 dependent. The rHDL-mediated increase in insulin secretion was ABCG1 dependent. Exposure of -cells to lipid-free apolipoproteins also increased insulin mRNA expression and insulin secretion without significantly depleting intracellular insulin or cholesterol levels. Conclusion—These results establish that lipid-free and
Arteriosclerosis, Thrombosis, and Vascular Biology – Wolters Kluwer Health
Published: Aug 1, 2010
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