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- Title
Direct and indirect effects of amino acids on hepatic glucose metabolism in humans M. Krebs et al.: Amino acids stimulate gluconeogenesis.
- Authors
Krebs, M.; Brehm, A.; Krssak, M.; Anderwald, C.; Bernroider, E.; Nowotny, P.; Roth, E.; Chandramouli, V.; Landau, B. R.; Waldhäusl, W.; Roden, M.
- Abstract
Aim/hypothesis. The study was designed to examine the contribution of direct (substrate-mediated) and indirect (hormone-mediated) effects of amino acids on hepatic glucose metabolism in healthy men. Methods. The protocols were: (i) CON+S (n=7): control conditions with somatostatin to inhibit endogenous hormone release resulting in fasting plasma concentrations of amino acids, insulin (~28 pmol/l) and glucagon (~65 ng/l), (ii) AA+S (n=7): amino acid infusion-fasting insulinaemia-fasting glucagonaemia, (iii) GLUC+S (n=6): fasting amino acids-fasting insulinaemia-hyperglucagonaemia (~99 ng/l) and (iv) AA-S (n=5): amino acid infusion without somatostatin resulting in amino acid-induced hyperinsulinaemia (~61 pmol/l)-hyperglucagonaemia (~147 ng/l). Net glycogenolysis was calculated from liver glycogen concentrations using 13C nuclear magnetic resonance spectroscopy. Total gluconeogenesis (GNG) was calculated by subtracting net glycogenolysis from endogenous glucose production (EGP) which was measured with [6,6-2H2]glucose. Net GNG was assessed with the 2H2O method. Results. During AA+S and GLUC+S, plasma glucose increased by about 50% (p<0.01) due to a comparable rise in EGP. This was associated with a 53-% (p<0.05) and a 65% increase (p<0.01) of total and net GNG during AA+S, whereas net glycogenolysis rose by 70% (p<0.001) during GLUC+S. During AA-S, plasma glucose remained unchanged despite nearly-doubled (p<0.01) total GNG. Conclusion/interpretation. Conditions of postprandial amino acid elevation stimulate secretion of insulin and glucagon without affecting glycaemia despite markedly increased gluconeogenesis. Impaired insulin secretion unmasks the direct gluconeogenic effect of amino acids and increases plasma glucose.
- Subjects
GLUCOSE; SUGARS; METABOLISM; AMINO acids; ORGANIC acids; BLOOD plasma
- Publication
Diabetologia, 2003, Vol 46, Issue 7, p917
- ISSN
0012-186X
- Publication type
Article
- DOI
10.1007/s00125-003-1129-1