The TRPA1 channel and oral hypoglycemic agents Is there complicity in β cell exhaustion?

Diabetes mellitus type 2 (DM2) results from the combination of insulin unresponsiveness in target tissues and the failure of pancreatic beta cells to secrete enough insulin.(1) It is a highly prevalent chronic disease that is aggravated with time, leading to major complications, such as cardiovascular disease and peripheral and ocular neuropathies.(2) Interestingly, therapies to improve glucose homeostasis in diabetic patients usually involve the use of glibenclamide, an oral hypoglycemic drug that blocks ATP-sensitive K+ channels (K-ATP),(3,4) forcing beta cells to release more insulin to overcome peripheral insulin resistance. However, sulfonylureas are ineffective for long-term treatments and ultimately result in the administration of insulin to control glucose levels.(5) The mechanisms underlying beta-cell failure to respond effectively with glibenclamide after long-term treatments still needs clarification. A recent study demonstrating that this drug activates TRPA1,(6) a member of the Transient Receptor Potential (TRP) family of ion channels and a functional protein in insulin secreting cells,(7,8) has highlighted a possible role for TRPA1 as a potential mediator of sulfonylurea-induced toxicity.