Telmisartan promotes insulin secretion in rats through direct inhibition of Kv2.1 channel
- VernacularTitle:替米沙坦通过直接抑制Kv2.1通道促进离体大鼠的胰岛素分泌
- Author:
Tao LIU
1
;
Xiao-Qin CHEN
;
Rui-Wang GUO
;
Li-Juan CUI
;
Shi-Wei LIU
Author Information
- Keywords: telmisartan; β-cell; insulin secretion; AT-1 receptor; PPARγ; Kv2.1 channel
- From: Chinese Pharmacological Bulletin 2024;40(5):893-898
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the signaling pathways related to telmisartan-induced insulinotropic effect in rats.Methods(1)Islets and cells were isolated from Wistar rats.Islets were treated with different drugs,then supernatant liquid was collected for insulin secretion.The changes in intracellular Ca2+([Ca2+]i)concentrations of β-cells and the effects on ion channel were observed using calcium imaging tech-nology and patch-clamp technology respectively.(2)CHO-Kv2.1 cell line was constructed with lentivirus vector overexpressing Kv2.1 channel,then patch-clamp experiment was performed on CHO-Kv2.1 cells to observe the direct effect of telmisartan on Kv2.1 channel.Results Different from telmisartan,valsar-tan and irbesartan under high glucose condition did not exhibit insulinotropic effect,elevation of[Ca2+]i lev-els,and inhibition of Kv channels in[3 cells.GW9662,a peroxisome proliferator-activated receptorγ(PPARγ)blocker,did not influence the effects of telmisartan on insulin secretion,[Ca2+]i level and Kv channel.CHO cells had no endogenous outward potas-sium currents,while Kv2.1 channel current and its concentration dependent suppression by telmisartan were both detected on CHO-Kv2.1 cells.Conclusion Neither AT-1 receptors nor PPARγ is involved in telmisartan-induced insulinotropic effect,and the effect of telmisartan is partly due to the direct inhibition of kv2.1 channel.
