Glucokinase is required for high-starch diet-induced β-cell mass expansion in mice

We aimed to determine whether glucokinase is required for β-cell mass expansion induced by high-starch diet (HSTD)-feeding, as has been shown in its high-fat diet-induced expansion.

Eight-week-old male wild-type (Gck^+/+ ) or glucokinase haploinsufficient (Gck^+/- ) mice were fed either a normal chow (NC) or an HSTD for 15 weeks. The bodyweight, glucose tolerance, insulin sensitivity, insulin secretion and β-cell mass were assessed.

Both HSTD-fed Gck^+/+ and Gck^+/- mice had significantly higher bodyweight than NC-fed mice. Insulin and oral glucose tolerance tests revealed that HSTD feeding did not affect insulin sensitivity nor glucose tolerance in either the Gck^+/+ or Gck^+/- mice. However, during the oral glucose tolerance test, the 15-min plasma insulin concentration after glucose loading was significantly higher in the HSTD group than that in the NC group for Gck^+/+ , but not for Gck^+/- mice. β-Cell mass was significantly larger in HSTD-fed Gck^+/+ mice than that in NC-fed Gck^+/+ mice. In contrast, the β-cell mass of the HSTD-fed Gck^+/- mice was not different from that of the NC-fed Gck^+/- mice.

The results showed that HSTD feeding would increase pancreatic β-cell mass and insulin secretion in Gck^+/+ , but not Gck^+/- mice. This observation implies that glucokinase in β-cells would be required for the increase in β-cell mass induced by HSTD feeding.