Abstract
OBJECTIVE: To investigate the effects of hyperglycaemia and hyperinsulinaemia on amino acid disposal in human obesity.
DESIGN: Four sequential experimental conditions: (1) overnight fasting; (2) hyperglycaemia with hyperinsulinaemia (2 h hyperglycaemic clamp at 11 mmol/l); (3) hyperglycaemia with basal insulin (1 h hyperglycaemic clamp during somatostatin infusion), (4) hyperglycaemia with resuming hyperinsulinaemia (1 h hyperglycaemic clamp after somatostatin discontinuation).
SUBJECTS: Seven non-obese and seven obese non-diabetic, normo-insulinaemic subjects.
MEASUREMENTS: Glucose infused to maintain steady-state hyperglycaemia. Plasma insulin, glucagon, free fatty acid and amino acid concentrations in the last 20 min of the four experimental conditions. Net rates of plasma amino acid disappearance and appearance (μmol/l per hour), calculated as the slopes of the regression of amino acid concentration on time.
RESULTS: The amount of glucose infused to maintain hyperglycaemia was reduced by nearly 50% in obese subjects. During hyperinsulinaemia, FFA suppression was lower in obese subjects. In all experimental conditions plasma amino acid levels were slightly, non-significantly higher in obese than in non-obese subjects. In both groups plasma amino acids decreased slightly with ongoing fasting, decreased remarkably during hyperglycaemia–hyperinsulinaemia, rose promptly when insulin concentration was suppressed by somatostatin infusion, and declined again after somatostatin discontinuation. Also the time-course of plasma branched-chain amino acids, which paralleled that of total amino acids, was similar in the two groups. The net rates of amino acid disappearance from plasma did not differ in obese and non-obese subjects both at fasting and during hyperglycaemia–hyperinsulinaemia. Also plasma amino acid appearance during hyperglycaemia with basal insulin was not different in the two groups.
CONCLUSION: The net traffic of amino acids to and from plasma in relation to insulin drive and prevailing glucose is not impaired in obese subjects with normal glucose tolerance, in spite of a decreased insulin sensitivity of glucose and lipid metabolism.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Groop LC, Ferrannini E . Insulin action and substrate competition Baillières Clin Endocrinol Metab 1993 4: 1007–1032.
DeFronzo RA . Insulin secretion, insulin resistance, and obesity Int J Obes 1982 6: 73–82.
Bonadonna RC, Bonora E . Glucose and free fatty acid metabolism in human obesity. Relationship to insulin resistance Diabetes Rev 1997 5: 21–51.
National Diabetes Data Group . Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance Diabetes 1979 28: 1039–1057.
Kolterman OG, Insel J, Saekow M, Olefsky JM . Mechanism of insulin resistance in human obesity. Evidence for receptor and post-receptor defects J Clin Invest 1980 83: 1272–1284.
Bonadonna RC, Groop L, Kraemer N, Ferrannini E, Del Prato S, DeFronzo RA . Obesity and insulin resistance in humans: a dose-response study Metabolism 1990 39: 452–459.
Bonora E, Moghetti P, Zancanaro C, Cigolini M, Querena M, Cacciatori V, Corgnati A, Muggeo M . Estimates of in vivo insulin action in man: comparison of insulin tolerance tests with euglycemic and hyperglycemic glucose clamp studies. J Clin Endocrinol Metab 1989 68: 374–378.
Zancanaro C, Cigolini M, Bonora E, Moghetti P, Cacciatori V, Querena M, Muggeo M . Plasma free fatty acid concentration during hyperglycemic glucose clamp with and without somatostatin infusion in obese subjects with normal glucose tolerance Int J Obesity 1990 14: 551–557.
Groop LC, Saloranta C, Shank M, Bonadonna RC, Ferranini E, De Fronzo RA . The role of free fatty acid metabolism in the pathogenesis of insulin resistance in obesity and noninsulin-dependent diabetes mellitus J Clin Endocrinol Metab 1991 72: 96–107.
Fukagawa NK, Minaker KL, Young VR, Rowe JW . Insulin dose-dependent reductions in plasma amino acids Am J Physiol 1986 250: E13–E17.
Berger M, Zimmerman-Telschov H, Bercthold P, Drost H, Müller WA, Griest A, Zimmerman H . Blood amino acid levels in patients with insulin excess (functioning insulinoma) and insulin deficiency (diabetic ketosis) Metabolism 1978 27: 793–799.
Felig P, Marliss E, Cahill GF . Plasma amino acid levels and insulin secretion in obesity N Engl J Med 1969 281: 811–816.
Adibi SA, Drash AL . Hormone and amino acid levels in altered nutritional states J Lab Clin Med 1970 76: 722–732.
Forlani G, Vannini P, Marchesini G, Zoli M, Ciavarella A, Pisi E . Insulin-dependent metabolism of branched-chain amino acids in obesity Metabolism 1984 33: 147–150.
Ashley DVM, Fleury MO, Golay A, Maeder E, Leathwood PD . Evidence for diminished 5-hydroxytryptamine biosynthesis in obese diabetic and nondiabetic humans Am J Clin Nutr 1985 42: 1240–1245.
Caballero B, Finer N, Wurtman RJ . Plasma amino acids and insulin levels in obesity response to carbohydrate intake and tryptophan supplements Metabolism 1988 37: 672–676.
Jensen MD, Haymond MW . Protein metabolism in obesity: effects of body fat distribution and hyperinsulinemia on leucine turnover Am J Clin Nutr 1991 53: 172–176.
Welle S, Barnard RR, Statt A, Amatruda JM . Increased protein turnover in obese women Metabolism 1992 41: 1028–1034.
Welle S, Statt M, Barnard R, Amatruda J . Differential effects of insulin on whole-body proteolysis and glucose metabolism in normal-weight, obese and reduced-obese women Metabolism 1994 43: 441–445.
Nair KS, Garrow JS, Ford C, Mahler RF, Halliday D . Effect of poor diabetic control and obesity on whole-body protein metabolism in man Diabetologia 1983 25: 400–403.
Nair KS, Halliday D, Ford GC, Heels S, Garrow JS . Failure of carbohydrate to spare leucine oxidation in obese subjects Int J Obes 1987 11: 537–544.
Bruce AC, McNurlan A, McHardy KC, Broom J, Buchanam KD, Calder AG, Milne E, McGaw BA, Garlick PJ, James WP . Nutrient oxidation patterns and protein metabolism in lean and obese subjects Int J Obes 1990 14: 631–646.
Caballero B, Wurtman RJ . Differential effects of insulin resistance on leucine and glucose kinetics in obesity Metabolism 1991 40: 51–58.
Luzi L, Castellino P, DeFronzo RA . Insulin and hyperaminoacidemia regulate by a different mechanism leucine turnover and oxidation in obesity Am J Physiol 1996 270: E273–E281.
Flakoll PJ, Hill JO, Abumrad NN . Acute hyperglycemia enhances proteolysis in normal man Am J Physiol 1993 265: E715–E721.
DeFronzo RA, Tobin JD, Andres R . Glucose clamp technique: a method for quantifying insulin secretion and resistance Am J Physiol 1979 28: E214–E223.
Marchesini G, Bianchi GP, Vilstrup H, Checchia GA, Patrono D, Zoli M . Plasma clearances of branched-chain amino acids in control subjects and in patients with cirrhosis J Hepatol 1987 4: 108–117.
Duncan DB . Multiple range test for correlated and heteroscedastic means Biometrics 1957 13: 164–204.
Bonora E, Del Prato S, Bonadonna RC, Gulli G, Solini A, Shank ML, Ghiatas AA, Lancaster JR, Kilcoyne RF, Alyassin AM, DeFronzo RA . Total body fat content and fat topography are differently associated with in vivo glucose metabolism in non-obese and obese non-diabetic women Diabetes 1992 41: 1151–1159.
Solini A, Bonora E, Bonadonna R, Castellino P, DeFronzo RA . Protein metabolism in human obesity: relationship with glucose and lipid metaboism and with visceral adipose tissue J Clin Endocrinol Metab 1997 82: 2252–2258.
Pijl H, Potter van Loon J, Toornvliet AC, Radder JK, Onkenhout W, Frolich M, Meinders AE . Insulin-induced decline of plasma amino acid concentrations in obese subjects with and without non-insulin dependent diabetes Metabolism 1994 43: 640–646.
Neely RD, Harper R, Rooney DP, Ennis CN, Bell PM, Trimble ER . Failure of complete suppression of endogenous glucose production by euglycemic hyperinsulinemia in normal humans Eur J Clin Invest 1995 25: 447–453.
Del Prato S, Bonadonna RC, Bonora E, Gulli G, Solini A, Shank M, De Fronzo RA . Characterization of cellular defects of insulin action in type 2 (non-insulin-dependent) diabetes mellitus J Clin Invest 1993 91: 484–494.
Moore MC, Connolly CC, Cherrington AD . Autoregulation of hepatic glucose production Eur J Endocrinol 1998 138: 240–248.
Rice DE, Flakoll PJ, May MM, Hill JO, Abumrad NN . The opposing effects of insulin and hyperglycemia in modulating amino acid metabolism during a glucose tolerance test in lean and obese subjects Metabolism 1994 43: 211–216.
Heiling VJ, Campbell PJ, Gottesman IS, Tsalikian E, Beaufrere B, Gerich JE, Haymond MW . Differential effects of hyperglycemia and hyperinsulinemia on leucine rate of appearance in normal humans J Clin Endocrinol Metab 1993 76: 203–206.
Wise S, Nielsen M, Rizza R . Effects of hepatic glycogen content on hepatic insulin action in humans: alteration in the relative contributions of glycogenolysis and gluconeogenesis to endogenous glucose production J Clin Endocrinol Metab 1997 82: 1828–1833.
Vilstrup H . Effects of glucose on alanine-derived urea synthesis Clin Physiol 1984 4: 495–507.
Boden G, Rezvanj I, Owen OE . Effects of glucagon on plasma amino acids J Clin Invest 1984 73: 785–793.
Hamberg O, Vilstrup H . Effects of glucose on hepatic conversion of aminonitrogen to urea in patients with cirrhosis: relationship to glucagon Hepatology 1994 19: 45–54.
Nair KS, Halliday D, Matthews DE, Welle SL . Hyperglucagonemia during insulin deficiency accelerates protein catabolism Am J Physiol 1987 253: E208–E213.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Marchesini, G., Bianchi, G., Rossi, B. et al. Effects of hyperglycaemia and hyperinsulinaemia on plasma amino acid levels in obese subjects with normal glucose tolerance. Int J Obes 24, 552–558 (2000). https://doi.org/10.1038/sj.ijo.0801195
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijo.0801195
Keywords
This article is cited by
-
Insulin resistance and the metabolism of branched-chain amino acids
Frontiers of Medicine (2013)
-
Excessive Energy Intake Does Not Modify Fed-state Tissue Protein Synthesis Rates in Adult Rats
Obesity (2009)