The calcium channel subunit gamma-4 is regulated by MafA and necessary for pancreatic beta-cell specification.

ABSTRACT: Voltage-gated Ca²⁺ (Ca_V) channels trigger glucose-induced insulin secretion in pancreatic beta-cell and their dysfunction increases diabetes risk. These heteromeric complexes include the main subunit alpha1, and the accessory ones, including subunit gamma that remains unexplored. Here, we demonstrate that Ca_V gamma subunit 4 (Ca_Vγ4) is downregulated in islets from human donors with diabetes, diabetic Goto-Kakizaki (GK) rats, as well as under conditions of gluco-/lipotoxic stress. Reduction of Ca_Vγ4 expression results in decreased expression of L-type Ca_V1.2 and Ca_V1.3, thereby suppressing voltage-gated Ca²⁺ entry and glucose stimulated insulin exocytosis. The most important finding is that Ca_V

SUBMITTER: Luan C 

PROVIDER: S-EPMC6420573 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature