Telmisartan potentiates insulin secretion via ion channels, independent of the AT1 receptor and PPARγ
Telmisartan potentiates insulin secretion via ion channels, independent of the AT1 receptor and PPARγ
Abstract Angiotensin II type 1 receptor blockers (ARBs), as antihypertensive drugs, have drawn attention for their benefits to individuals with diabetes and prediabetes. However, the effects of ARBs on insulin secretion remain unclear. Here, we investigated the insulinotropic effects of ARBs (telmisartan, valsartan, and irbesartan) and the underlying electrophysiological mechanism in rat islets. We found that only telmisartan among the three ARBs exhibited an insulin secretagogue role. Distinct from other ARBs, 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 in a glucose-dependent manner. We observed that the peroxisome proliferator-activated receptor γ pathway was not involved in these telmisartan-induced effects. Furthermore, we identified that telmisartan at least directly inhibited Kv2.1 channel through construction of a Chinese hamster ovary cell line with Kv2.1 channel overexpression. Acute exposure of type 2 diabetes model (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. We further observed the telmisartan-induced insulinotropic and electrophysiological effects on pathological pancreatic islets isolated from db/db mice. Collectively, our results establish an important function of telmisartan distinct from other ARBs in the treatment of diabetes.
Liu Tao、Xue Huan、Zhi Linping、Liu Mengmeng、Bai Tao、Liu Zhihong、He Peifeng、Guo Qing、Yang Huanhuan、Zhang Yi、Zhang Min、Liu Yunfeng、Cui Lijuan、Yang Xiaohua
Department of Pharmacology, School of Basic Medicine, Shanxi Medical University||Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University||Department of General Surgery, Shanxi Bethune HospitalDepartment of Pharmacology, School of Basic Medicine, Shanxi Medical University||Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical UniversityDepartment of Pharmacology, School of Basic Medicine, Shanxi Medical UniversityDepartment of Pharmacology, School of Basic Medicine, Shanxi Medical UniversityDepartment of Pharmacology, School of Basic Medicine, Shanxi Medical University||Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University||Department of Endocrinology, the First Affiliated Hospital of Shanxi Medical UniversityDepartment of Pharmacology, School of Basic Medicine, Shanxi Medical University||Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical UniversitySchool of Management, Shanxi Medical UniversityDepartment of Pharmacology, School of Basic Medicine, Shanxi Medical UniversityDepartment of Pharmacology, School of Basic Medicine, Shanxi Medical UniversityDepartment of Pharmacology, School of Basic Medicine, Shanxi Medical University||Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical UniversitySchool of Pharmacy, Shanxi Medical UniversityDepartment of Endocrinology, the First Affiliated Hospital of Shanxi Medical UniversityDepartment of Pharmacology, School of Basic Medicine, Shanxi Medical University||Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical UniversityDepartment of Pharmacology, School of Basic Medicine, Shanxi Medical University
药学基础医学生理学
telmisartaninsulin secretionAT1 receptorPPARγKv channel
Liu Tao,Xue Huan,Zhi Linping,Liu Mengmeng,Bai Tao,Liu Zhihong,He Peifeng,Guo Qing,Yang Huanhuan,Zhang Yi,Zhang Min,Liu Yunfeng,Cui Lijuan,Yang Xiaohua.Telmisartan potentiates insulin secretion via ion channels, independent of the AT1 receptor and PPARγ[EB/OL].(2025-03-28)[2025-05-05].https://www.biorxiv.org/content/10.1101/2020.09.20.305334.点此复制
评论