[en] Elevated free fatty acid concentrations are known to decrease insulin-mediated glucose uptake, glucose oxidation and glycogen synthesis. In order to determine whether free fatty acids inhibit glycogen synthesis at the level of liver cells, the effects of an infusion of lipids on carbohydrate metabolism were investigated in healthy subjects during a two-step (16.7 and 33.4 mumol/(kg.min) 13C-fructose infusion. Fructose infusion dose-dependently stimulated fructose (measured from 13CO2 production) and net carbohydrate oxidation (measured with indirect calorimetry). It also stimulated systemic 13C glucose appearance, indicating a dose-dependent stimulation of gluconeogenesis. Net glucose output (measured with 6,6 2H glucose) was however not altered. Lipid infusion significantly reduced fructose oxidation (measured from 13CO2 production) at both rates of fructose infusion, but did not alter plasma fructose or lactate concentrations, nor plasma 13C glucose appearance or net glucose production. Non oxidative fructose disposal was increased by 31% (p < 0.05) at the lowest, and by 18% (p < 0.01) at the highest infusion rate. Since nonoxidative fructose disposal corresponds mainly to liver glycogen deposition, these results suggest that lipid infusion increased hepatic glycogen synthesis, and hence that hepatic glycogen synthase is not inhibited by fatty acids.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Surmely, J. F.
Paquot, Nicolas ; Centre Hospitalier Universitaire de Liège - CHU > Diabétologie,nutrition, maladies métaboliques
Schneiter, P.
Jequier, E.
Temler, E.
Tappy, L.
Language :
English
Title :
Non oxidative fructose disposal is not inhibited by lipids in humans.
Randle P, Garland P, Hales C, Newsholme E. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet, 1963, 1, 785-9.
Gomez F, Jéquier E, Chabot V, Buber V, Felber JP. Carbohydrate and lipid oxidation in normal human subjects: its influence on glucose tolerance and insulin response to glucose. Metabolism, 1972, 21, 381-391.
Ferrannini E, Barrett EJ, Bevilacqua S, DeFronzo RA. Effect of fatty acids on glucose production and utilization in man. J Clin Invest, 1983, 72, 1737-1747.
Boden G, Chen X, Ruiz J, White JV, Rossetti L. Mechanisms of fatty acid-induced inhibition of glucose uptake. J Clin Invest, 1994, 93, 2438-2446.
Randle PJ, Priestman DA, Mistry S, Halsall A. Mechanisms modifying glucose oxidation in diabetes mellitus. Diabetologia, 1994, 37 (Suppl. 2), S155-S161.
Thiébaud D, DeFronzo RA, Jacot E, . Effect of long-chain triglyceride infusion on glucose metabolism in man. Metabolism, 1982, 31, 1128-1136.
Boden G, Jadali F. Effects of lipid on basal carbohydrate metabolism in normal men. Diabetes, 1991, 40, 686-692.
Rebrin K, Steil GM, Mittelman SD, Bergman RN. Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs. J Clin Invest, 1996, 98, 741-749.
Nuutila P, Koivisto VA, Knuuti J, . Glucose-free fatty acid cycle operates in human heart and skeletal muscle in vivo. J Clin Invest, 1992, 89, 1767-1774.
Roden M, Price TB, Perseghin G, et al. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest, 1996, 97, 2859-2865.
Vaag AA, Handberg A, Skott P, Richter EA, Beck-Nielsen H. Glucose-fatty acid cycle operates in humans at the levels of both whole body and skeletal muscle during low andn high physiological plasma insulin concentrations. Eur J Endocrinol, 1994, 130, 70-79.
Mayes PA. Intermediary metabolism of fructose. Am J Clin Nutr, 1993, 58 (suppl), 754S-765S.
Tappy L, Randin JP, Felber JP, et al. Comparison of thermogenic effect of fructose and glucose in normal humans. Am J Physiol, 1986, 250, E718-E724.
Nilsson LH, Hultman E. Liver and muscle glycogen in man after glucose and fructose infusion. Scand J Clin Lab Invest, 1974, 33, 5-10.
Gay LJ, Schneiter P, Schutz Y, et al. A non invasive assessment of hepatic glycogen kinetics and post-absorptive gluconeogenesis in man. Diabetologia, 1994, 37, 517-523.
Schmidt FH. Die enzymatische Bestimmung von Glucose und Fructose nebeneinander. Klin Wochenschrift, 1961, 39, 1244-1247.
Wolfe RR: Radioactive and stable isotope tracers in biomedicine. New York, Wiley-Liss, 1992.
Proietto J, Rohner-Jeanrenaud F, Ionescu E, et al. Non-steady-state measurement of glucose turnover in rats by using a one-compartment model. Am J Physiol, 1987, 252, E77-E84.
Tappy L, Owen O, Boden G. Effect of hyperinsulinemia on urea pool size and substrate oxidation rates. Diabetes, 1988, 37, 1212-1217.
Livesey G, Elia M. Estimation of energy expenditure, net carbohydrate utilization, and net fat oxidation and synthesis by indirect calorimetry; evaluation of errors with special reference to the detailed composition of foods. Am J Clin Nutr, 1988, 47, 608-628.
Tounian P, Schneiter P, Henry S, Jéquier E, Tappy L. Effects of infused fructose on endogenous glucose production, gluconeogenesis and glycogen metabolism in healthy humans. Am J Physiol, 1994, 267, E710-E717.
Vaag A, Skött P, Damsbo P, et al. Effect of the antilipolytic nicotinic acid analog acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus. J Clin Invest, 1991, 88, 1282-1290.
Vaag A, Damsbo P, Hother-Nielsen O, Beck-Nielsen H. Hyperglycaemia compensates for the defects in insulin-mediated glucose metabolism and in the activation of glycogen synthase in the skeletal muscle of patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia, 1992, 35, 80-88.
Saloranta C, Franssila-Kallunki A, Ekstrand A, Taskinen M-R, Groop L. Modulation of hepatic glucose production by non-esterified fatty acids in Type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia, 1991, 34, 409-415.
Björkman O, Gunnarsson R, Hagström E, Felig P, Wahren J. Splanchnic and renal exchange of infused fructose in insulin-deficient type 1 diabetic patients and healthy controls. J Clin Invest, 1989, 83, 52-59.
Shulman G, Rothman D, Jue T, et al. Quantitation of muscle glycogen synthesis in normal subjects and in subjects with non-insulin dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med, 1990, 322, 223-28.
Tounian P, Schneiter P, Henry S, Delarue J, Tappy L. Effects of dexamethasone on hepatic glucose production and fructose metabolism in healthy humans. Am J Physiol, 1997, 273, E315-E320.
Paquot N, Schneiter P, Jéquier E, et al. Effects of ingested fructose and infused glucagon on endogenous glucose production in obese NIDDM patients, obese non-diabetic subjects, and healthy subjects. Diabetologia, 1996, 39, 580-586.
Delarue J, Normand S, Couet C, et al. Effects of free fatty acids on the metabolic response to oral fructose in lean healthy humans. Int J Obes, 1996, 20, 130-136.
Vollenweider P, Tappy L, Randin D, et al. Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans. J Clin Invest, 1993, 92, 147-154.
Boden G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes, 1997, 46, 3-10.
Groop C, Bonadonna R, Shank M, Petrides A, DeFronzo R. Role of free fatty acids and insulin in determining free fatty acid and lipid oxidation in man. J Clin Invest, 1991, 87, 83-89.
Groop L, Eriksson J, Ekstrand A, et al. Metabolic characteristics of autoimmune diabetes mellitus in adults. Diabetologia, 1991, 34, 46-51.
Yki-Jarvinen H, Puhakainen I, Saloranta C, Groop L, Taskinen MR. Demonstration of a novel feedback mechanism between FFA oxidation from intracellular and intravascular sources. Am J Physiol, 1991, 260, E680-E689.
Schwarz JM, Neese R, Shackleton C, Hellerstein MK. De novo lipogenesis during fasting and oral fructose in lean and obese hyperinsulinemic subjects. Diabetes, 1993, 42, Suppl. 1, 39A (Abstr.).
Flatt JP: The biochemistry of energy expenditure, in: Bray GA (ed.): Recent Advances in Obesity Research, London, Newman Publishing, 1978, 2, 211-228.
