Quantification of gluconeogenesis in cirrhosis: Response to glucagon

Background & Aims: Accelerated starvation and early recruitment of alternat e fuels in cirrhosis have been attributed to reduced availability of hepati c glycogen, The aim of this study was to measure gluconeogenesis (as a mark er of protein oxidation) in relation to total glucose production and glucag on-stimulated glycogenolysis, Methods: Glucose and urea production, glucone ogenesis, and glycogenolysis were calculated using stable isotope methods b efore and during glucagon infusion (3 ng.kg(-1).min(-1)) in 5 cirrhotic pat ients and 5 matched controls before and after glycogen repletion. Results: In the basal state, cirrhotic patients had a normal rate of glucose product ion, but the contribution of gluconeogenesis was increased (74.3% +/- 4.1% vs. 55.6% +/- 12.1%; P < 0.005). Glycogen repletion normalized the rate of gluconeogenesis. The glycemic response to glucagon (3 ng.kg(-1).min(-1)) wa s blunted in cirrhotic patients because of a lower rate of glycogenolysis ( 0.63 +/- 0.23 vs. 1.22 +/- 0.23 mg.kg(-1).min(-1); P < 0.01) and was not af fected by glycogen repletion. Despite increased gluconeogenesis, the simult aneously measured rate of urea synthesis was lower in cirrhotic patients (3 .11 +/- 1.02 vs. 5.0 +/- 1.0 mg/kg; P < 0.05). Conclusions: These data show that in cirrhosis, glucose production is sustained by an increased rate of gluconeogenesis. The hepatic resistance to glucagon action is not caused b y reduced glycogen stores.