Inhibition of mitochondrial fatty acid oxidation in vivo only slightly suppresses gluconeogenesis but enhances clearance of glucose in mice
Autor: | Terry G J Derks, Folkert Kuipers, G. Peter A. Smit, Aldo Grefhorst, Jan Peter Rake, Theo H. van Dijk, Dirk-Jan Reijngoud |
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Přispěvatelé: | Center for Liver, Digestive and Metabolic Diseases (CLDM), Experimental Vascular Medicine, Vascular Medicine, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism |
Jazyk: | angličtina |
Rok vydání: | 2008 |
Předmět: |
FLUX
medicine.medical_specialty Pyruvate dehydrogenase kinase Pyruvate Kinase RAT-LIVER Mitochondria Liver Biology DEFICIENT MICE HEPATIC GLUCONEOGENESIS Mice Internal medicine Glucokinase medicine Animals Glycolysis RNA Messenger Beta oxidation ISOTOPOMER DISTRIBUTION ANALYSIS DE-NOVO SYNTHESIS Hepatology INSULIN SENSITIVITY Fatty Acids Gluconeogenesis Fasting Metabolism Mice Inbred C57BL De novo synthesis Glucose Endocrinology Liver CARNITINE PALMITOYL TRANSFERASE Glucose-6-Phosphatase Epoxy Compounds 2-TETRADECYLGLYCIDIC ACID BETA-OXIDATION Oxidation-Reduction Pyruvate kinase |
Zdroj: | Hepatology, 47(3), 1032-1042. Wiley Hepatology, 47(3), 1032-1042. John Wiley and Sons Ltd |
ISSN: | 1527-3350 0270-9139 |
DOI: | 10.1002/hep.22101 |
Popis: | Mitochondrial fatty acid oxidation (mFAO) is considered to be essential for driving gluconeogenesis (GNG) during fasting. However, quantitative in vivo data on de novo synthesis of glucose-6-phosphate upon acute inhibition of mFAO are lacking. We assessed hepatic glucose metabolism in vivo after acute inhibition of mFAO by 30 mg kg(-1) 2-tetradecylglycidic acid (TDGA) in hypoketotic hypoglycemic male C57BL/6J mice by the infusion of [U-C-13]glucose, [2-C-13]glycerol, [1-H-2] galactose, and paracetamol for 6 hours, which was followed by mass isotopomer distribution analysis in blood glucose and urinary paracetamol-glucuronide. During TDGA treatment, endogenous glucose production was unaffected (127 +/- 10 versus 118 +/- 7 mu mol kg(-1) minute(-1), control versus TDGA, not significant), but the metabolic clearance rate of glucose was significantly enhanced (15.9 +/- 0.9 versus 26.3 +/- 1.1 mL kg(-1) minute(-1), control versus TDGA, P |
Databáze: | OpenAIRE |
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