Alteration of De Novo Glucose Production Contributes to Fasting Hypoglycaemia in Fyn Deficient Mice

• DOI: 10.1371/journal.pone.0081866
• Publication Date: 2013-11-28T21:18:18Z
• Authors: Yingjuan Yang; Elena Tarabra; Gong-She Yang; Bhavapriya Vaithe...; Gustavo Palacios; Irwin J. Kurland; Jeffrey E. Pessin; Claire C. Bastie
• Keywords: Fructokinase; Glucokinase; Glycerol kinase; Dihydroxyacetone phosphate; Glyceraldehyde; Gluconeogenesis; Carbohydrate Metabolism; Aldolase B

Previous studies have demonstrated that glucose disposal is increased in the Fyn knockout (FynKO) mice due to insulin sensitivity. FynKO also display fasting hypoglycaemia despite decreased levels, which suggested hepatic production was unable compensate for basal utilization. The present study investigates basis reduction plasma levels and reduced ability liver produce response gluconeogenic substrates. had a 5-fold phosphoenolpyruvate carboxykinase (PEPCK) gene protein expression marked pyruvate, pyruvate/lactate-stimulated output. Remarkably, de novo blunted using substrates bypass PEPCK step. Impaired conversion of glycerol observed both tolerance test determination 13C-glycerol fasted state. α-glycerol phosphate were but kinase not changed. Fructose-driven diminished without alteration fructokinase levels. normal dihydroxyacetone glyceraldehyde-3-phosphate extracts triose function. Fructose-bisphosphate aldolase (aldolase) mRNA or Fyn-deficient livers, however, there large fructose-6-phosphate (30-fold) fructose-1,6-bisphosphate (7-fold) as well glucose-6-phosphate (2-fold) These data suggest mechanistic defect allosteric regulation activity.