Cellular characterisation of the GCKR P446L variant associated with type 2 diabetes risk.

ABSTRACT:

Aims/hypothesis

Translation of genetic association signals into molecular mechanisms for diabetes has been slow. The glucokinase regulatory protein (GKRP; gene symbol GCKR) P446L variant, associated with inverse modulation of glucose- and lipid-related traits, has been shown to alter the kinetics of glucokinase (GCK) inhibition. As GCK inhibition is associated with nuclear sequestration, we aimed to determine whether this variant also alters the direct interaction between GKRP and GCK and their intracellular localisation.

Methods

Fluorescently tagged rat and human wild-type (WT)- or P446L-GCKR and GCK were transiently transfected into HeLa cells and mouse primary hepatocytes. Whole-cell and nuclear fluorescence was quantified in individual cells exposed to low- or high-gluco

SUBMITTER: Rees MG 

PROVIDER: S-EPMC3276843 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature