This study was performed to test the ability of HDLs and their main apolipoproteins, apolipoprotein AI and AII, to regulate pancreatic β-cell insulin secretion. In vitro studies were conducted on Min6 cells and primary islets from Sprague-Dawley rats under basal or high-glucose conditions. The results revealed that apolipoprotein AI and AII, in either lipid-free form or as a constituent of discoidal reconstituted HDLs, markedly increase insulin secretion from Min6 cells and primary islets. This was observed under basal (2.8 mmol/l glucose) and high-glucose (25 mmol/l) conditions. Human HDL at physiological concentration also increased insulin secretion under basal condition. Moreover, the results indicate that apolipoprotein AI and AII increase insulin secretion from β-cells by 2 distinct mechanisms. Under high-glucose conditions, the mechanism involved potassium ATP channel activation, glucose metabolism and calcium mobilization. Under basal conditions, lipid-free apolipoproteins accentuated insulin secretion through a calcium-dependent pathway that was independent of glucose metabolism and potassium ATP channel. It was also observed that the ability of lipid-free apolipoprotein AI and AII to increase insulin secretion depended on ATP binding cassette (ABC) transporter A1 and scavenger receptor-B1 expression, and on ABCG1 expression in the case of discoidal rHDL. These results suggest that interventions that raise HDL levels could possibly be used in the prevention of type 2 diabetes. In their editorial comment, Getz GS and Reardon CA described the results of the study by Fryirs et al. and recognized the interesting findings concerning the possible mechanisms to explain the association between HDL components and β-cell insulin secretion.
Documentation centre