Caveolin-1 is essential for glimepiride-induced insulin secretion in the pancreatic βTC-6 cell line

Abstract: The KATP channels play a pivotal role in the complex mechanism of insulin secretion. KATP channels represent the target of sulphonylureas, a class of drugs widely used in type 2 diabetes to stimulate insulin secretion. We previously showed that caveolin-1 depletion impairs action of the sulphonylurea glimepiride in human endothelial cells. The aim of this work was to investigate the possible role of caveolin-1 in glimepiride-induced insulin secretion. Caveolin-1 was depleted using siRNA method in the pancreatic βTC-6 cell line. Then stimulation of insulin secretion was performed with different secretagogues (glucose, KCl, and glimepiride). Here, we show that βTC-6 caveolin-1 depleted cells maintained high rate of insulin secretion after KCl, but not after glucose and glimepiride stimulation. Moreover, we find a direct interaction between caveolin-1 and Kir6.2, one of the KATP channel subunit. These results demonstrate that Cav-1 plays a critical role for glucose and sulfonylurea-stimulated insulin secretion. [Copyright &y& Elsevier]