title: Prevention of diabetic alterations in transgenic mice overexpressing Myc in the liver.
abstract: Recent studies have demonstrated that the overexpression of the c-myc gene in the liver of transgenic mice leads to an increase in both utilization and accumulation of glucose in the liver, suggesting that c-Myc transcription factor is involved in the control of liver carbohydrate metabolism in vivo. To determine whether the increase in c-Myc might control glucose homeostasis, an intraperitoneal glucose tolerance test was performed. Transgenic mice showed lower levels of blood glucose than control animals, indicating that the overexpression of c-Myc led to an increase of blood glucose disposal by the liver. Thus, the increase in c-Myc might counteract diabetic hyperglycemia. In contrast to control mice, transgenic mice treated with streptozotocin showed normalization of concentrations of blood glucose, ketone bodies, triacylglycerols and free fatty acids in the absence of insulin. These findings resulted from the normalization of liver metabolism in these animals. While low glucokinase activity was detected in the liver of diabetic control mice, high levels of both glucokinase mRNA and enzyme activity were noted in the liver of streptozotocin-treated transgenic mice, which led to an increase in intracellular levels of glucose 6-phosphate and glycogen. The liver of these mice also showed an increase in pyruvate kinase activity and lactate production. Furthermore, normalization of both the expression of genes involved in the control of gluconeogenesis and ketogenesis and the production of glucose and ketone bodies was observed in streptozotocin-treated transgenic mice. Thus, these results suggested that c-Myc counteracted diabetic alterations through its ability to induce hepatic glucose uptake and utilization and to block the activation of gluconeogenesis and ketogenesis.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Riu
authors.forename: F
authors.initials: F
authors.lastname: Bosch
authors.forename: A
authors.initials: A
authors.lastname: Valera
mesh_terms: D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015870:Gene Expression; D016259:Genes, myc; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2; D006019:Glycolysis; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000235:genetics; D007657:Ketone Bodies / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D013311:Streptozocin; D014444:Tyrosine Transaminase / Q000235:genetics
chemical_list: D051273:Glucose Transporter Type 2; D007657:Ketone Bodies; D009004:Monosaccharide Transport Proteins; D013311:Streptozocin; D002334:Carnitine O-Palmitoyltransferase; D006904:Hydroxymethylglutaryl-CoA Synthase; D014444:Tyrosine Transaminase; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D019764:Phosphoenolpyruvate Carboxykinase (ATP); D005947:Glucose