17beta-Estradiol modulates apoptosis in pancreatic beta-cells by specific involvement of the sulfonylurea receptor (SUR) isoform SUR1.

Apoptosis of pancreatic beta-cells is an important factor in the pathophysiology of diabetes. Previously, we have shown that the "phytoestrogen" resveratrol can induce beta-cell apoptosis dependent on the expression of sulfonylurea receptor (SUR) 1, the regulatory subunit of pancreatic ATP-sensitive K(+) channels. Here, we investigate whether 17beta-estradiol also influences beta-cell apoptosis in a SUR1-dependent manner.

Resveratrol binds to the sulfonylurea receptor (SUR) and induces apoptosis in a SUR subtype-specific manner.

Sulfonylurea receptors (SURs) constitute the regulatory subunits of ATP-sensitive K+ channels (K(ATP) channels). SUR binds nucleotides and synthetic K(ATP) channel modulators, e.g.

Glibenclamide-induced apoptosis is specifically enhanced by expression of the sulfonylurea receptor isoform SUR1 but not by expression of SUR2B or the mutant SUR1(M1289T).

Sulfonylurea receptor 1 (SUR1) is the regulatory subunit of the pancreatic ATP-sensitive K+ channel (K(ATP) channel), which is essential for triggering insulin secretion via membrane depolarization. Sulfonylureas, such as glibenclamide and tolbutamide, act as K(ATP) channel blockers and are widely used in diabetes treatment. These antidiabetic substances are known to induce apoptosis in pancreatic beta-cells or beta-cell lines under certain conditions.