Impaired Glucose Tolerance and Predisposition to the Fasted State in Liver Glycogen Synthase Knock-out Mice

摘要: Conversion to glycogen is a major fate of ingested glucose in the body. A rate-limiting enzyme synthesis synthase encoded by two genes, GYS1, expressed muscle and other tissues, GYS2, primarily liver (liver synthase). Defects GYS2 cause inherited monogenic disease storage 0. We have generated mice with liver-specific disruption Gys2 gene knock-out (LGSKO) mice), using Lox-P/Cre technology. Conditional carrying floxed were crossed expressing Cre recombinase under albumin promoter. The resulting LGSKO are viable, develop deficiency, 95% reduction fed content. They mild hypoglycemia but dispose less well tolerance test. Fed, also reduced capacity for exhaustive exercise compared alleles, difference disappears after an overnight fast. Upon fasting, reach within 4 h decreased blood levels attained control only 24 food deprivation. maintain this low at least h. Basal gluconeogenesis increased mice, insulin suppression endogenous production impaired as assessed euglycemic-hyperinsulinemic clamp. This observation correlates increase gluconeogenic phosphoenolpyruvate carboxykinase expression activity. mouse model mimics pathophysiology 0 patients highlights importance stores whole body homeostasis.