High-Fat Diet-Fed Kcnq1 Mutant Mice Have Reduced Pancreatic β-Cell Mass via Gene-Environment Interaction.

ABSTRACT:

Backgruound

The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic β-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA 'Kcnq1ot1,' which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic β-cell failure; however, the degree

SUBMITTER: Asahara SI 

PROVIDER: S-EPMC12813374 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature