Deletion of CDKAL1 affects high-fat diet-induced fat accumulation and glucose-stimulated insulin secretion in mice, indicating relevance to diabetes.

ABSTRACT:

Background/objective

The CDKAL1 gene is among the best-replicated susceptibility loci for type 2 diabetes, originally identified by genome-wide association studies in humans. To clarify a physiological importance of CDKAL1, we examined effects of a global Cdkal1-null mutation in mice and also evaluated the influence of a CDKAL1 risk allele on body mass index (BMI) in Japanese subjects.

Methods

In Cdkal1-deficient (Cdkal1⁻/⁻) mice, we performed oral glucose tolerance test, insulin tolerance test, and perfusion experiments with and without high-fat feeding. Based on the findings in mice, we tested genetic association of CDKAL1 variants with BMI, as a measure of adiposity, and type 2 diabetes in Japanese.

Principal findings

On a standard diet, Cdkal1⁻/⁻ mice were modestl

SUBMITTER: Okamura T 

PROVIDER: S-EPMC3500257 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature