Diabetes, Vol 42, Issue 12 1868-1877, Copyright © 1993 by American Diabetes Association

ARTICLES

Different sensitivity of glucose and amino acid metabolism to insulin in NIDDM

L Luzi, AS Petrides and RA De Fronzo
Department of Internal Medicine, University of Texas Health Science Center, San Antonio 78284.

NIDDM subjects are characterized by impaired glucose tolerance and insulin resistance with respect to glucose metabolism. To examine whether the defect in glucose utilization extends to amino acid metabolism, 6 NIDDM subjects (64 +/- 4 yr of age; ideal body weight of 107 +/- 3%) and 7 control subjects (58 +/- 4 yr of age; ideal body weight of 105 +/- 2%) were studied with the euglycemic insulin clamp technique, in combination with [1-14C]leucine and indirect calorimetry. All subjects participated in two studies. In study 1, after 3 h of tracer equilibration, a 3-h insulin clamp (40 mU.m-2 x min-1) was performed to define the effect of insulin on leucine kinetics and glucose metabolism. In study 2, subjects received a repeat 3-h insulin clamp, and a balanced amino acid solution was infused to increase the plasma amino acid concentrations approximately 2-fold to examine the effect of combined physiological hyperinsulinemia-hyperaminoacidemia on the rate of leucine and glucose disposal. Insulin-mediated total body glucose uptake was significantly reduced in NIDDM during both study 1 (5.6 +/- 0.4 vs. 6.9 +/- 0.6 mg.kg-1 x min-1, P < 0.01) and study 2 (5.2 +/- 0.4 vs. 6.8 +/- 0.6, P < 0.01). Basal plasma leucine (120 +/- 10 vs. 123 +/- 11 microM) and alpha-ketoisocaproic acid concentrations (28 +/- 3 vs. 25 +/- 2 microM) were similar in NIDDM and control subjects, respectively. In contrast, the basal plasma glucose concentration (8.9 +/- 0.8 vs. 4.7 +/- 0.2 microM) and the HbA1c (8.5 +/- 0.2 vs. 5.7 +/- 0.2%) were significantly increased in NIDDM (P < 0.01). In the postabsorptive state, endogenous leucine flux, leucine oxidation, and nonoxidative leucine disposal were similar in NIDDM and control subjects. When insulin was infused without amino acids (study 1), the decrement in plasma leucine (53 +/- 5 vs. 48 +/- 4 microM), endogenous leucine flux (13 +/- 2 vs. 11 +/- 1 mumol.m-2 x min-1), leucine oxidation (1.6 +/- 0.2 vs. 1.3 +/- 0.1 mumol.m-2 x min-1), and nonoxidative leucine disposal (10 +/- 1 vs. 8 +/- 1 mumol.m-2 x min-1) was comparable in both groups. During combined insulin and amino acid infusion (study 2), plasma leucine concentration (185 +/- 20 vs. 190 +/- 15 microM) rose similarly in NIDDM and control subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. Moller and K. S. Nair Diabetes and Protein Metabolism Diabetes, January 1, 2008; 57(1): 3 - 4. [Full Text] [PDF]

				S. Pereira, E. B. Marliss, J. A. Morais, S. Chevalier, and R. Gougeon Insulin Resistance of Protein Metabolism in Type 2 Diabetes Diabetes, January 1, 2008; 57(1): 56 - 63. [Abstract] [Full Text] [PDF]

				K. C Maki, T. M Rains, V. N Kaden, K. R Raneri, and M. H Davidson Effects of a reduced-glycemic-load diet on body weight, body composition, and cardiovascular disease risk markers in overweight and obese adults Am. J. Clinical Nutrition, March 1, 2007; 85(3): 724 - 734. [Abstract] [Full Text] [PDF]

				D. N. Reeds, W. T. Cade, B. W. Patterson, W. G. Powderly, S. Klein, and K. E. Yarasheski Whole-Body Proteolysis Rate Is Elevated in HIV-Associated Insulin Resistance. Diabetes, October 1, 2006; 55(10): 2849 - 2855. [Abstract] [Full Text] [PDF]

				J. A. Bell, E. Volpi, S. Fujita, J. G. Cadenas, M. Sheffield-Moore, and B. B. Rasmussen Skeletal Muscle Protein Anabolic Response to Increased Energy and Insulin Is Preserved in Poorly Controlled Type 2 Diabetes J. Nutr., May 1, 2006; 136(5): 1249 - 1255. [Abstract] [Full Text] [PDF]

				P. Tessari, A. Coracina, E. Kiwanuka, M. Vedovato, M. Vettore, A. Valerio, M. Zaramella, and G. Garibotto Effects of Insulin on Methionine and Homocysteine Kinetics in Type 2 Diabetes With Nephropathy Diabetes, October 1, 2005; 54(10): 2968 - 2976. [Abstract] [Full Text] [PDF]

				C. Guillet, A. Zangarelli, P. Gachon, B. Morio, C. Giraudet, P. Rousset, and Y. Boirie Whole Body Protein Breakdown Is Less Inhibited by Insulin, But Still Responsive to Amino Acid, in Nondiabetic Elderly Subjects J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6017 - 6024. [Abstract] [Full Text] [PDF]

				G. Lattuada, L. P. Sereni, D. Ruggieri, A. Scollo, S. Benedini, F. Ragogna, F. Costantino, A. Battezzati, L. Luzi, and G. Perseghin Postabsorptive and Insulin-Stimulated Energy Homeostasis and Leucine Turnover in Offspring of Type 2 Diabetic Patients Diabetes Care, November 1, 2004; 27(11): 2716 - 2722. [Abstract] [Full Text] [PDF]

				R. Barazzoni, E. Kiwanuka, M. Zanetti, M. Cristini, M. Vettore, and P. Tessari Insulin Acutely Increases Fibrinogen Production in Individuals With Type 2 Diabetes but Not in Individuals Without Diabetes Diabetes, July 1, 2003; 52(7): 1851 - 1856. [Abstract] [Full Text] [PDF]

				P. Halvatsiotis, K. R. Short, M. Bigelow, and K. S. Nair Synthesis Rate of Muscle Proteins, Muscle Functions, and Amino Acid Kinetics in Type 2 Diabetes Diabetes, August 1, 2002; 51(8): 2395 - 2404. [Abstract] [Full Text] [PDF]

				R. Sreekumar, P. Halvatsiotis, J. C. Schimke, and K. S. Nair Gene Expression Profile in Skeletal Muscle of Type 2 Diabetes and the Effect of Insulin Treatment Diabetes, June 1, 2002; 51(6): 1913 - 1920. [Abstract] [Full Text] [PDF]

				A. P. Richardson and J. A. Tayek Type 2 diabetic patients may have a mild form of an injury response: a clinical research center study Am J Physiol Endocrinol Metab, June 1, 2002; 282(6): E1286 - E1290. [Abstract] [Full Text] [PDF]

				S. Benedini, R. Fiocchi, A. Battezzati, P. Scifo, L. P. Sereni, A. Gamba, C. Mammana, A. Del Maschio, G. Perseghin, and L. Luzi Energy Metabolism in Diabetic and Nondiabetic Heart Transplant Recipients Diabetes Care, March 1, 2002; 25(3): 530 - 536. [Abstract] [Full Text] [PDF]

				Y. Boirie, P. Gachon, N. Cordat, P. Ritz, and B. Beaufrère Differential Insulin Sensitivities of Glucose, Amino Acid, and Albumin Metabolism in Elderly Men and Women J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 638 - 644. [Abstract] [Full Text]

				L. Luzi, G. Perseghin, M. D. Brendel, I. Terruzzi, A. Battezzati, M. Eckhard, D. Brandhorst, H. Brandhorst, S. Friemann, C. Socci, et al. Metabolic Effects of Restoring Partial {beta}-Cell Function After Islet Allotransplantation in Type 1 Diabetic Patients Diabetes, February 1, 2001; 50(2): 277 - 282. [Abstract] [Full Text]

				Y. Schutz, C. M Rueda-Maza, M. Zaffanello, and C. Maffeis Whole-body protein turnover and resting energy expenditure in obese, prepubertal children Am. J. Clinical Nutrition, May 1, 1999; 69(5): 857 - 862. [Abstract] [Full Text] [PDF]

				P. De Feo Fed State Protein Metabolism in Diabetes Mellitus J. Nutr., February 1, 1998; 128(2): 328 - 328. [Abstract] [Full Text]

				A. Solini, E. Bonora, R. Bonadonna, P. Castellino, and R. A. DeFronzo Protein Metabolism in Human Obesity: Relationship with Glucose and Lipid Metabolism and with Visceral Adipose Tissue J. Clin. Endocrinol. Metab., August 1, 1997; 82(8): 2552 - 2558. [Abstract] [Full Text] [PDF]