Caveolin-1 is essential for glimepiride-induced insulin secretion in the pancreatic betaTC-6 cell line.
The K(ATP) channels play a pivotal role in the complex mechanism of insulin secretion. K(ATP) 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 betaTC-6 cell line. Then stimulation of insulin secretion was performed with different secretagogues (glucose, KCl, and glimepiride). Here, we show that betaTC-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 K(ATP) channel subunit. These results demonstrate that Cav-1 plays a critical role for glucose and sulfonylurea-stimulated insulin secretion.
Puddu
A
A
Department of Internal Medicine, University of Genova, Genova, Italy.
Salani
B
B
Cordera
R
R
Viviani
G L
GL
Maggi
D
D
D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D000099161:Kcnj11 Channel
D051242:Caveolin 1; D007004:Hypoglycemic Agents; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D034741:RNA, Small Interfering; D013453:Sulfonylurea Compounds; D000099161:Kcnj11 Channel; C057619:glimepiride