Effects of High-Density Lipoproteins on Pancreatic Beta-Cell Insulin Secretion

Type 2 diabetes is characterized by impaired beta-cell secretory function, insulin resistance, reduced high-density lipoprotein (HDL) levels, and increased cardiovascular risk. Given the current interest in therapeutic interventions that raise HDL levels, this study investigated the effects of HDL on insulin secretion from beta-cells.

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 HDL (rHDL), or with HDL 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_ATP channel and glucose metabolism dependent under 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 ß-cells to lipid-free apolipoproteins also increased insulin mRNA expression and insulin secretion without significantly depleting intracellular insulin or cholesterol levels.

From the results it was established that lipid-free and lipid-associated apoA-I and apoA-II increase beta-cell insulin secretion and indicate that interventions that raise HDL levels may be beneficial in Type 2 diabetes.

Arteriosclerosis, Thrombosis, and Vascular Biology. Online May 13, 2010, doi: 10.1161/ATVBAHA.110.207373