Wee, Jungwon Pak, Sungmin Kim, Tahnbee Hong, Gyu-Sang Lee, Ji Seon Nan, Jinyan Kim, Hyungsup Lee, Mi-Ock Park, Kyong Soo Oh, Uhtaek 2024-01-19T13:31:15Z 2024-01-19T13:31:15Z 2022-04-03 2021-11 2211-1247 https://pubs.kist.re.kr/handle/201004/116164 Glucose homeostasis is initially regulated by the pancreatic hormone insulin. Glucose-stimulated insulin secretion in beta-cells is composed of two cellular mechanisms: a high glucose concentration not only depolarizes the membrane potential of the beta-cells by ATP-sensitive K+ channels but also induces cell inflation, which is sufficient to release insulin granules. However, the molecular identity of the stretch-activated cation channel responsible for the latter pathway remains unknown. Here, we demonstrate that Tentonin 3/TMEM150C (TTN3), a mechanosensitive channel, contributes to glucose-stimulated insulin secretion by mediating cation influx. TTN3 is expressed specifically in beta-cells and mediates cation currents to glucose and hypotonic stimulations. The glucose-induced depolarization, firing activity, and Ca2+ influx of beta-cells were significantly lower in Ttn3(-/-) mice. More importantly, Ttn3(-/-) mice show impaired glucose tolerance with decreased insulin secretion in vivo. We propose that TTN3, as a stretch-activated cation channel, contributes to glucose-stimulated insulin secretion. English Cell Press Tentonin 3/TMEM150C regulates glucose-stimulated insulin secretion in pancreatic beta-cells Article 10.1016/j.celrep.2021.110067 1 Cell Reports, v.37, no.9 Cell Reports 37 9 Y scie scopus 000725686500004 2-s2.0-85119920210 Cell Biology Cell Biology Article SENSITIVE K+ CHANNELS ELECTRICAL-ACTIVITY DIABETES-MELLITUS CALCIUM RELEASE VOLUME DYSFUNCTION ACTIVATION KNOCKOUT ISLETS beta cell diabetes mellitus insulin mechanosensitive channel pancreas Tentonin 3