Elevated glucose metabolism triggers two primary processes that lead toβ-cell depolarization and insulin secretion:the closure of ATPsensitive K+channels via ATP-dependent mechanisms and the activation of mechanosens...Elevated glucose metabolism triggers two primary processes that lead toβ-cell depolarization and insulin secretion:the closure of ATPsensitive K+channels via ATP-dependent mechanisms and the activation of mechanosensitive channels(MSCs)due to cell swelling.However,the identity of these MSCs remains unclear.In this study,we found that TMEM63B is a stretch-activated cation channel(SAC)crucial for regulating insulin secretion in response to elevated glucose levels.TMEM63B is abundantly expressed inβ-cells,and its deletion impairs insulin secretion triggered by high glucose.High glucose levels typically increase Ca2+influx and firing frequency inβ-cells,a response largely eliminated when TMEM63B is deleted.Mechanistically,glucose metabolism induces cell swelling and activates TMEM63B,which,in turn,leads toβ-cell depolarization and insulin secretion.In conclusion,our findings demonstrate that TMEM63B is an SAC essential for regulating insulin secretion in response to elevated glucose levels.展开更多
基金supported by grants from the National Natural Science Foundation of China(32330044 and 32170951 to Y.S.S.,82201615 to X.Y.T.,and 82271891 to J.C.)the Guangdong High Level Innovation Research Institute(2021B0909050004 to Y.S.S.)+2 种基金the National Key R&D Program of China(2019YFA0801603 to Y.S.S.)the Natural Science Foundation of Jiangsu Province(BK20240251 to C.Y.)the Fundamental Research Funds for the Central Universities(02141438053 to Y.S.S)。
文摘Elevated glucose metabolism triggers two primary processes that lead toβ-cell depolarization and insulin secretion:the closure of ATPsensitive K+channels via ATP-dependent mechanisms and the activation of mechanosensitive channels(MSCs)due to cell swelling.However,the identity of these MSCs remains unclear.In this study,we found that TMEM63B is a stretch-activated cation channel(SAC)crucial for regulating insulin secretion in response to elevated glucose levels.TMEM63B is abundantly expressed inβ-cells,and its deletion impairs insulin secretion triggered by high glucose.High glucose levels typically increase Ca2+influx and firing frequency inβ-cells,a response largely eliminated when TMEM63B is deleted.Mechanistically,glucose metabolism induces cell swelling and activates TMEM63B,which,in turn,leads toβ-cell depolarization and insulin secretion.In conclusion,our findings demonstrate that TMEM63B is an SAC essential for regulating insulin secretion in response to elevated glucose levels.
