Glucokinase Inactivation Paradoxically Ameliorates Glucose Intolerance by Increasing ?-Cell Mass in <i>db/db</i> Mice

Efficacy of glucokinase activation on glycemic control is limited to a short-term period. One reason might be related excess glucose signaling by toward ?-cells. In this study, we investigated the effect haploinsufficiency tolerance as well ?-cell function and mass using mouse model type 2 diabetes. Our results showed that in db/db mice with haploinsufficiency, was ameliorated augmented insulin secretion associated increase when compared mice. Gene expression profiling immunohistochemical metabolomic analyses revealed islets lower stress-related genes, greater transcription factors involved maintenance maturation function, less mitochondrial damage, superior metabolic pattern. These effects could preserve under diabetic conditions. findings verified our hypothesis optimizing ?-cells inhibiting prevent insufficiency, leading improving diabetes status preserving mass. Therefore, inactivation ?-cells, paradoxically, potential strategy for treatment