Tentonin 3/TMEM150C regulates glucose-stimulated insulin secretion in pancreatic β-cells.

Glucose homeostasis is initially regulated by the pancreatic hormone insulin. Glucose-stimulated insulin secretion in β-cells is composed of two cellular mechanisms: a high glucose concentration not only depolarizes the membrane potential of the β-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 β-cells and mediates cation currents to glucose and hypotonic stimulations. The glucose-induced depolarization, firing activity, and Ca ²⁺ influx of β-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.
Competing Interests: Declaration of interests U.O. and J.W. have a registered patent in the Republic of Korea for the use of Tentonin 3 for developing treatments of diabetes mellitus (KR-10-2019-0083428).
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)