Endoplasmic reticulum stress in beta cells: latent mechanism of secondary sulfonylurea failure in type 2 diabetes?

Sulfonylureas, by stimulating beta cell to secrete insulin, are still largely used for treatment of type 2 diabetic patients. More recently concern has been raised with respect to possible adverse effects associated with the use of these agents, like favoring beta cell apoptosis and beta cell exhaustion, which is believed as the reason for high rate secondary sulfonylurea failure. Endoplasmic reticulum (ER) stress often occurred when load of client protein exceed the folding capacity in secretory cell. Here, we hypothesize that overstimulation by chronic use of sulfonylureas could probably leads to ER stress and finally apoptosis in beta cell, which might be the latent mechanism for secondary sulfonylurea failure.