Mechanism of Glucagon Activation of Gluconeogenesis
1971; Elsevier BV; Linguagem: Inglês
10.1016/b978-0-12-654350-6.50020-2
AutoresJohn H. Exton, M Ui, Stephen B. Lewis, C.R. Park,
Tópico(s)Pharmacology and Obesity Treatment
ResumoThe gluconeogenic action of glucagon was studied in rat livers perfused with bicarbonate buffer containing bovine albumin and red cells. In livers from fed rat perfused with 20 mM 14C-lactate, glucagon increased the formation of 14C-glucose plus 14C-glycogen approximately two-fold but did not alter the production of 14CO2 or 14C-ketone bodies. The 14C-lactate uptake was increased by 28% and the labeling of lipids and proteins was decreased by approximately 40%. Oxygen consumption, ketogenesis, ureogenesis and glycogenolysis were also increased. The data are consistent with the activation of gluconeogenesis from lactate and endogenous sources (probably protein). There was no evidence of inhibition of lactate oxidation. Acetyl-CoA production from endogenous substrate (probably lipid) appeared to be increased resulting in increased ketogenesis and a reduction in the specific activity of 14C-ketone bodies. The radioactivity of cholesterol and fatty acid esters was decreased to an extent corresponding to the reduction in acetyl-CoA specific activity, suggesting that glucagon did not inhibit cholesterol and fatty acid synthesis. The increase in respiration was greater than that attributable to increased ketogenesis and protein catabolism indicating that the Krebs cycle was activated. The extra substrate utilized in the cycle was apparently derived from endogenous sources.
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