Sulfonylurea induced beta-cell apoptosis in cultured human islets

摘要: Loss of beta-cell mass and function raises a concern regarding the application sulfonylureas for treatment type 2 diabetes because previous studies have shown that agents cause closure inwardly rectifying K(+) sulfonylurea receptor subtype ATP-sensitive potassium channels, such as tolbutamide glibenclamide, induce apoptosis in lines rodent islets. Therefore, we investigated effect new insulin secretagogues, repaglinide nateglinide, sulfonylurea, on human Human islets from six organ donors were cultured onto extracellular matrix-coated plates exposed to repaglinide, or nateglinide. The doses three compounds chosen according detected maximal effects, i.e. efficacy. Exposure 4 h 0.1 10 microm glibenclamide induced 2.09- 2.46-fold increase apoptosis, respectively, whereas (0.01 1 microm) did not change number apoptotic beta-cells. At low concentration (10 microm), nateglinide apoptosis. However, at high 1000 microm, it 1.49-fold Prolonged exposure d secretagogues was 3.71- 4.4-fold 2.37- 3.8-fold 0.01 3.2- 4.6-fold respectively. Glibenclamide 0.1-10 nm (doses less efficient secretion) after incubation well incubation. 2.24- 2.53-fold Taken together, channels induces may precipitate decrease observed patients with diabetes.