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Horm Metab Res 2001; 33(2): 89-95
DOI: 10.1055/s-2001-12403
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

A Novel Use of the Hyperinsulinemic-Euglycemic Clamp Technique to Estimate Insulin Sensitivity of Systemic Lipolysis

M. Stumvoll1 , H. G. Wahl1 , K. Löblein, R. Becker, A. Volk, W. Renn, S. Jacob, H. Häring
  • Department of Endocrinology and Metabolism, Eberhard-Karls-Universität, Tübingen, Germany
  • 1 These authors contributed equally to the study
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Publication History

Publication Date:
31 December 2001 (online)

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The aim of the present study was to assess whether a standard hyperinsulinemic-euglycemic clamp can provide an estimate for the antilipolytic insulin sensitivity. For this purpose, we infused 9 non-obese, healthy volunteers with [2H5]glycerol and used the glycerol rate of appearance (Ra) in plasma as an index for systemic lipolysis during a standard (1 mU/kg · min, 120 min) and a 3-step (0.1, 0.25, 1.0 mU/kg · min) hyperinsulinemic-euglycemic clamp. The insulin concentration, which half-maximally suppressed lipolysis (EC50) in the three-step clamp, was considered to be the gold standard for the antilipolytic insulin sensitivity. Glycerol Ra decreased from 1.53 ± 0.11 µmol/kg·min to 0.60 ± 0.09 µmol/kg · min (p < 0.001) during the standard clamp. The decrease in Ra at most time points during the standard clamp significantly correlated with the EC50. The highest correlation for the % decrease of glycerol Ra from baseline was found at 60 min (r = 0.96, p < 0.001) making this parameter a useful index for the antilipoytic insulin sensitivity. Neither plasma glycerol nor plasma free fatty acid (FFA) concentrations were significantly correlated with the EC50. In conclusion, the standard hyperinsulinemic-euglycemic clamp in combination with isotopic determination of glycerol Ra provides a reasonable estimate for the antilipolytic insulin sensitivity. In healthy subjects, the parameter best suited to estimate the insulin EC50 (by linear correlation) was the percentage decrease of glycerol Ra at 60 min.

Key words:

Insulin Resistance - Obesity - Type 2 Diabetes - Free Fatty Acids - Glycerol

References

  • 1 Bonadonna R C, Bonora E. Glucose and free fatty acid metabolism in human obesity.  Diabetes Rev. 1997;  5 21-51
    PubMedGoogle Scholar
  • 2 Campbell P J, Carlson M G, Nurjhan N. Fat metabolism in human obesity.  Am J Physiol. 1994;  266 E600-E605
    PubMedGoogle Scholar
  • 3 Groop L C, Bonadonna R C, Simonson D C, Petrides A S, Shank M, DeFronzo R A. Effect of insulin on oxidative and nonoxidative pathways of free fatty acid metabolism in human obesity.  Am J Physiol. 1992;  263 E79-E84
    PubMedGoogle Scholar
  • 4 Groop L C, Bonadonna R C, DelPrato S, Ratheiser K, Zyck K, Ferrannini E, DeFronzo R A. Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance.  J Clin Invest. 1989;  84 205-213
    PubMedGoogle Scholar
  • 5 Randle P J, Priestman D A, Mistry S C, Halsall A. Glucose fatty acid interactions and the regulation of glucose disposal.  J Cell Biol. 1994;  55S 1-11
    PubMedGoogle Scholar
  • 6 Boden G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM.  Diabetes. 1997;  46 3-10
    PubMedGoogle Scholar
  • 7 Paolisso G, Howard B V. Role of non-esterified fatty acids in the pathogenesis of type 2 diabetes.  Diabetic Med. 1998;  15 360-366
    PubMedGoogle Scholar
  • 8 Eriksson J W, Smith U, Waagstein F, Wysocki M, Jansson P. Glucose turnover and adipose tissue lipolysis are insulin-resistant in healthy relatives of type 2 diabetes patients. Is cellular insulin resistance a secondary phenomenon?.  Diabetes. 1999;  48 1572-1578
    PubMedGoogle Scholar
  • 9 Ferrannini E, Camastra S, Coppack S W, Fliser D, Golay A, Mitrakou A. Insulin action and non-esterified fatty acids. The European Group for the Study of Insulin Resistance (EGIR).  Proc Nutr Soc. 1997;  56 753-761
    PubMedGoogle Scholar
  • 10 Pimenta W, Korytkowski M, Mitrakou A, Jenssen T, Yki-Järvinen H, Evron W, Dailey G, Gerich J. Pancreatic beta-cell dysfunction as the primary genetic lesion in NIDDM.  JAMA. 1995;  273 1855-1861
    PubMedGoogle Scholar
  • 11 Pan D A, Lillioja S, Kriketos A D, Milner M R, Baur L A, Bogardus C, Jenkins A B, Storlien L H. Skeletal muscle triglyceride levels are inversely related to insulin action.  Diabetes. 1997;  46 983-988
    PubMedGoogle Scholar
  • 12 Nyholm B, Qu Z, Kaal A, Pedersen S B, Gravholt C H, Andersen J L, Saltin B, Schmitz O. Evidence of an increased number of type IIb muscle fibers in insulin-resistant first-degree relatives of patients with NIDDM.  Diabetes. 1997;  46 1822-1828
    PubMedGoogle Scholar
  • 13 Volk A, Renn W, Overkamp D, Mehnert B, Maerker E, Jacob S, Balletshofer B, Häring H U, Rett K. Insulin action and secretion in healthy, glucose tolerant first degree relatives of patients with type 2 diabetes. Influence of body weight.  Exp Clin Endocrinol Diabetes. 1999;  107 140 -147
    PubMedGoogle Scholar
  • 14 Townsend R R, Klein S, Wolfe R R. Changes in lipolytic sensitivity following repeated epinephrine infusion in humans.  Am J Physiol. 1994;  266 E155-E160
    PubMedGoogle Scholar
  • 15 Nurjhan N, Campbell P, Kennedy F, Miles J, Gerich J. Insulin dose-response characteristics for suppression of glycerol release and conversion to glucose in humans.  Diabetes. 1986;  35 1326-1331
    PubMedGoogle Scholar
  • 16 Robinson C, Tamborlane W V, Maggs D G, Enoksson S, Sherwin R S, Silver D, Shulman G I, Caprio S. Effect of insulin on glycerol production in obese adolescents.  Am J Physiol. 1998;  274 E737-E743
    PubMedGoogle Scholar
  • 17 Stumvoll M, Jacob S. Multiple sites of insulin resistance: muscle, liver and adipose tissue.  Exp Clin Endocrinol Diabetes. 1999;  107 107-110
    PubMedGoogle Scholar
  • 18 Hagström-Toft E, Bolinder J, Ungerstedt U, Arner P. A circadian rhythm in lipid mobilization which is altered in IDDM.  Diabetologia. 1997;  40 1070-1078
    PubMedGoogle Scholar
  • 19 Campbell P J, Carlson M G, Hill J O, Nurjhan N. Regulation of free fatty acid metabolism by insulin in humans: role of lipolysis and reesterification.  Am J Physiol. 1992;  263 E1063-E1069
    PubMedGoogle Scholar
  • 20 DeBodo R, Steele R, Atszuler N, Dunn A, Bishop J. On the hormonal regulation of carbohydrate metabolism: studies with C14 glucose.  Rec Prog Horm Res. 1963;  19 445-488
    PubMedGoogle Scholar
  • 21 McCulloch A J, Johnston D G, Baylis P H, Kendall Taylor P, Clark F, Young E T, Alberti K G. Evidence that thyroid hormones regulate gluconeogenesis from glycerol in man.  Clin Endocrinol Oxf. 1983;  19 67-76
    PubMedGoogle Scholar
  • 22 Beylot M, Martin C, Beaufrère B, Riou J P, Mornex R. Determination of steady state and nonsteady-state glycerol kinetics in humans using deuterium-labeled tracer.  J Lipid Res. 1987;  28 414-422
    PubMedGoogle Scholar
  • 23 Diaconis P, Efron B. Computer-intensive methods in statistics.  Scientific American. 1983;  248 116-132
    PubMedGoogle Scholar
  • 24 Saggerson E D, Greenbaum A L. The regulation of triglyceride synthesis and fatty acid synthesis in rat epididymal adipose tissue.  Biochem J. 1970;  119 193-219
    PubMedGoogle Scholar
  • 25 Reaven G, Chang H, Hoffman B B. Impaired insulin-mediated inhibition of lipolysis and glucose transport with aging.  Horm Metab Res. 1989;  21 168-171
    PubMedGoogle Scholar
  • 26 Finegood D T, Bergman R N, Vranic M. Estimation of endogenous glucose production during hyperinsulinemic-euglycemic glucose clamps. Comparison of unlabeled and labeled exogenous glucose infusates.  Diabetes. 1987;  36 914-924
    PubMedGoogle Scholar
  • 27 Stumvoll M, Welle S, Chintalapudi U, Perriello G, Gutierrez O, Gerich J. Uptake and release of glucose by the human kidney: Postabsorptive rates and responses to epinephrine.  J Clin Invest. 1995;  96 2528-2533
    PubMedGoogle Scholar
  • 28 Kellerer M, Rett K, Renn W, Groop L, Häring H U. Circulating TNF-alpha and leptin levels in offspring of NIDDM patients do not correlate to individual insulin sensitivity.  Horm Metab Res. 1996;  28 737-743
    PubMedGoogle Scholar
  • 29 Coppack S W, Persson M, Judd R L, Miles J M. Glycerol and nonesterified fatty acid metabolism in human muscle and adipose tissue.  Am J Physiol. 1999;  276 E233-E240
    PubMedGoogle Scholar

Dr. M. Stumvoll

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