Genetic activation of α-cell glucokinase in mice causes enhanced glucose-suppression of glucagon secretion during normal and diabetic states.

ABSTRACT:

Objective

While the molecular events controlling insulin secretion from β-cells have been documented in detail, the exact mechanisms governing glucagon release by α-cells are understood only partially. This is a critical knowledge gap, as the normal suppression of glucagon secretion by elevated glucose levels fails in type 2 diabetes (T2D) patients, contributing to hyperglycemia through stimulation of hepatic glucose production. A critical role of glycolytic flux in regulating glucagon secretion was supported by recent studies in which manipulation of the activity and expression of the glycolytic enzyme glucokinase altered the setpoint for glucose-suppression of glucagon secretion (GSGS). Given this precedent, we hypothesized that genetic activation of glucokinase specifically in α

SUBMITTER: Bahl V 

PROVIDER: S-EPMC7973249 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature