Journal of Clinical Endocrinology & Metabolism, Vol 77, 27-32, Copyright © 1993 by Endocrine Society

ARTICLES

Expression of the major insulin regulatable glucose transporter (GLUT4) in skeletal muscle of noninsulin-dependent diabetic patients and healthy subjects before and after insulin infusion

PH Andersen, S Lund, H Vestergaard, S Junker, BB Kahn and O Pedersen
Division of Endocrinology and Metabolism, University Clinic of Internal Medicine C, Aarhus, Denmark.

In a cross-sectional study we have examined the regulatory effect of insulin in vivo on the major insulin regulatable glucose transporter (GLUT4) in vastus lateralis muscle from 12 noninsulin-dependent diabetes mellitus (NIDDM) patients and 8 healthy control subjects. Insulin-stimulated glucose uptake rate in peripheral tissue was decreased by 41% (P < 0.01) in NIDDM patients compared to healthy subjects, whereas no significant differences could be shown in the abundance of total GLUT4 protein per DNA or GLUT4 messenger RNA (mRNA) per DNA among the 2 groups in muscle biopsies obtained in the basal state. In healthy subjects, 4 h of insulin infusion (2 mU/kg/min) induced a 31% reduction (P < 0.05) in the total GLUT4 protein content per DNA and a 35% increase (P < 0.05) in GLUT4 mRNA per DNA, whereas the GLUT4 mRNA and protein responses to insulin were heterogenous and statistically unaltered in the NIDDM patients. The GLUT4 protein per DNA of muscle obtained in the basal state correlated positively with the in vivo insulin-stimulated glucose uptake rate in the control group (r = 0.82, P < 0.05), whereas there was no comparable correlation in the NIDDM group (r = 0.05, P = 0.88). Furthermore, GLUT4 protein content in skeletal muscle after 4 h of insulin infusion did not correlate with insulin-stimulated glucose uptake in any of the groups. In conclusion, 4 h of insulin infusion causing supraphysiological serum insulin levels modulates the expression of GLUT4 in skeletal muscle from healthy subjects, with divergent effects at protein and mRNA levels. The physiological significance of these observations will have to be elucidated in future studies. Factors other than total GLUT4 protein content of muscle play a role in determining insulin-stimulated glucose uptake in human skeletal muscle.

This article has been cited by other articles:

				S. L. McGee, B. J.W. van Denderen, K. F. Howlett, J. Mollica, J. D. Schertzer, B. E. Kemp, and M. Hargreaves AMP-Activated Protein Kinase Regulates GLUT4 Transcription by Phosphorylating Histone Deacetylase 5 Diabetes, April 1, 2008; 57(4): 860 - 867. [Abstract] [Full Text] [PDF]

				F. W. Booth and S. J. Lees Fundamental questions about genes, inactivity, and chronic diseases Physiol Genomics, January 17, 2007; 28(2): 146 - 157. [Abstract] [Full Text] [PDF]

				Y. W. Asmann, C. S. Stump, K. R. Short, J. M. Coenen-Schimke, Z. Guo, M. L. Bigelow, and K. S. Nair Skeletal Muscle Mitochondrial Functions, Mitochondrial DNA Copy Numbers, and Gene Transcript Profiles in Type 2 Diabetic and Nondiabetic Subjects at Equal Levels of Low or High Insulin and Euglycemia Diabetes, December 1, 2006; 55(12): 3309 - 3319. [Abstract] [Full Text] [PDF]

				D. J. Padilla, P. McDonough, B. J. Behnke, Y. Kano, K. S. Hageman, T. I. Musch, and D. C. Poole Effects of Type II diabetes on capillary hemodynamics in skeletal muscle Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2439 - H2444. [Abstract] [Full Text] [PDF]

				H. Storgaard, P. Poulsen, C. Ling, L. Groop, and A. A. Vaag Genetic and Nongenetic Determinants of Skeletal Muscle Glucose Transporter 4 Messenger Ribonucleic Acid Levels and Insulin Action in Twins J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 702 - 708. [Abstract] [Full Text] [PDF]

				L. J. Cluberton, S. L. McGee, R. M. Murphy, and M. Hargreaves Effect of carbohydrate ingestion on exercise-induced alterations in metabolic gene expression J Appl Physiol, October 1, 2005; 99(4): 1359 - 1363. [Abstract] [Full Text] [PDF]

				N. Jessen, C. B. Djurhuus, J. O. L. Jorgensen, L. S. Jensen, N. Moller, S. Lund, and O. Schmitz Evidence against a role for insulin-signaling proteins PI 3-kinase and Akt in insulin resistance in human skeletal muscle induced by short-term GH infusion Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E194 - E199. [Abstract] [Full Text] [PDF]

				S. Rome, K. Clement, R. Rabasa-Lhoret, E. Loizon, C. Poitou, G. S. Barsh, J.-P. Riou, M. Laville, and H. Vidal Microarray Profiling of Human Skeletal Muscle Reveals That Insulin Regulates ~800 Genes during a Hyperinsulinemic Clamp J. Biol. Chem., May 9, 2003; 278(20): 18063 - 18068. [Abstract] [Full Text] [PDF]

				S. Lemosquet, E. Debras, M. Balage, J. F. Hocquette, H. Rulquin, and J. Grizard Short-term mild hyperglycemia enhances insulin-stimulated glucose disposal in lactating goats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2002; 282(2): R464 - R474. [Abstract] [Full Text] [PDF]

				D. Jaquet, H. Vidal, R. Hankard, P. Czernichow, and C. Levy-Marchal Impaired Regulation of Glucose Transporter 4 Gene Expression in Insulin Resistance Associated with in UteroUndernutrition J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3266 - 3271. [Abstract] [Full Text] [PDF]

				P.-H. Ducluzeau, N. Perretti, M. Laville, F. Andreelli, N. Vega, J.-P. Riou, and H. Vidal Regulation by Insulin of Gene Expression in Human Skeletal Muscle and Adipose Tissue: Evidence for Specific Defects in Type 2 Diabetes Diabetes, May 1, 2001; 50(5): 1134 - 1142. [Abstract] [Full Text]

				A. Thorell, J. Nygren, M. F. Hirshman, T. Hayashi, K. S. Nair, E. S. Horton, L. J. Goodyear, and O. Ljungqvist Surgery-induced insulin resistance in human patients: relation to glucose transport and utilization Am J Physiol Endocrinol Metab, April 1, 1999; 276(4): E754 - E761. [Abstract] [Full Text] [PDF]

				J. P. Jones and G. L. Dohm Regulation of glucose transporter GLUT-4 and hexokinase II gene transcription by insulin and epinephrine Am J Physiol Endocrinol Metab, October 1, 1997; 273(4): E682 - E687. [Abstract] [Full Text] [PDF]

				S. Asp, A. Watkinson, N. D. Oakes, and E. W. Kraegen Prior eccentric contractions impair maximal insulin action on muscle glucose uptake in the conscious rat J Appl Physiol, April 1, 1997; 82(4): 1327 - 1332. [Abstract] [Full Text] [PDF]

				S. Asp and E. A. Richter Decreased insulin action on muscle glucose transport after eccentric contractions in rats J Appl Physiol, November 1, 1996; 81(5): 1924 - 1928. [Abstract] [Full Text] [PDF]