Gluco-incretins regulate beta-cell glucose competence by epigenetic silencing of Fxyd3 expression.

ABSTRACT:

Background/aims

Gluco-incretin hormones increase the glucose competence of pancreatic beta-cells by incompletely characterized mechanisms.

Methods

We searched for genes that were differentially expressed in islets from control and Glp1r-/-; Gipr-/- (dKO) mice, which show reduced glucose competence. Overexpression and knockdown studies; insulin secretion analysis; analysis of gene expression in islets from control and diabetic mice and humans as well as gene methylation and transcriptional analysis were performed.

Results

Fxyd3 was the most up-regulated gene in glucose incompetent islets from dKO mice. When overexpressed in beta-cells Fxyd3 reduced glucose-induced insulin secretion by acting downstream of plasma membrane depolarization and Ca++ influx. Fxyd3 expression

SUBMITTER: Vallois D 

PROVIDER: S-EPMC4110016 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature