Telmisartan potentiates insulin secretion via ion channels, independent of the AT1 receptor and PPARγ

Angiotensin II type 1 receptor blockers (ARBs) have drawn attention for their benefits to individuals with diabetes and prediabetes. However, the effects of ARBs on insulin secretion remain clear. Here, we investigated the insulinotropic effects of ARBs (telmisartan, valsartan, and irbesartan) in rat islets. We found that only telmisartan among the three ARBs exhibited an insulin secretagogue role. Independentof AT1 receptor and peroxisome proliferator-activated receptor γ, telmisartan exerted effects on ion channels including voltage-gated potassium (Kv) channels and voltage-gated Ca2+ channels to promote extracellular Ca2+ influx, thereby potentiating insulin secretion glucose-dependently. Furthermore, we identified telmisartan at least directly inhibited Kv2.1 channel. Acute exposure of db/db mice to a telmisartan dose equivalent to therapeutic doses in humans resulted in lower blood glucose and increased plasma insulin concentration in the oral glucose tolerance test. Collectively, our results establish an important function of telmisartan distinct from other ARBs in the treatment of diabetes.