BACKGROUND & AIMS: Accelerated starvation and early recruitment of alternate fuels in cirrhosis have been attributed to reduced availability of hepatic glycogen. The aim of this study was to measure gluconeogenesis (as a marker of protein oxidation) in relation to total glucose production and glucagon-stimulated glycogenolysis. METHODS: Glucose and urea production, gluconeogenesis, and glycogenolysis were calculated using stable isotope methods before and during glucagon infusion (3 ng. kg-1. min-1) in 5 cirrhotic patients and 5 matched controls before and after glycogen repletion. RESULTS: In the basal state, cirrhotic patients had a normal rate of glucose production, 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) was 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 affected by glycogen repletion. Despite increased gluconeogenesis, the simultaneously 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 by reduced glycogen stores.
BACKGROUND & AIMS: Accelerated starvation and early recruitment of alternate fuels in cirrhosis have been attributed to reduced availability of hepatic glycogen. The aim of this study was to measure gluconeogenesis (as a marker of protein oxidation) in relation to total glucose production and glucagon-stimulated glycogenolysis. METHODS:Glucose and urea production, gluconeogenesis, and glycogenolysis were calculated using stable isotope methods before and during glucagon infusion (3 ng. kg-1. min-1) in 5 cirrhotic patients and 5 matched controls before and after glycogen repletion. RESULTS: In the basal state, cirrhotic patients had a normal rate of glucose production, 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) was 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 affected by glycogen repletion. Despite increased gluconeogenesis, the simultaneously 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 by reduced glycogen stores.
Authors: Inmaculada López-Flores; Juan B Barroso; Raquel Valderrama; Francisco J Esteban; Esther Martínez-Lara; Francisco Luque; M Angeles Peinado; Hirofumi Ogawa; José A Lupiáñez; Juan Peragón Journal: Mol Cell Biochem Date: 2005-01 Impact factor: 3.396
Authors: Christopher Scott; Rebecca Stokes; Kuan Minn Cha; Andrew Clouston; Mohammed Eslam; Mayda Metwally; Michael M Swarbrick; Jacob George; Jenny E Gunton Journal: PLoS One Date: 2019-12-04 Impact factor: 3.240
Authors: E Bugianesi; A Gastaldelli; E Vanni; R Gambino; M Cassader; S Baldi; V Ponti; G Pagano; E Ferrannini; M Rizzetto Journal: Diabetologia Date: 2005-03-04 Impact factor: 10.122
Authors: Pamela S Tietz-Bogert; Minsuk Kim; Angela Cheung; James H Tabibian; Julie K Heimbach; Charles B Rosen; Madhumitha Nandakumar; Konstantinos N Lazaridis; Nicholas F LaRusso; Jaeyun Sung; Steven P O'Hara Journal: Int J Mol Sci Date: 2018-10-16 Impact factor: 5.923