Diabetes, Vol 44, Issue 8 936-946, Copyright © 1995 by American Diabetes Association

ARTICLES

Insulin action and glucose metabolism in nondiabetic control and NIDDM subjects. Comparison using human skeletal muscle cell cultures

RR Henry, L Abrams, S Nikoulina and TP Ciaraldi
Department of Medicine, University of California, San Diego, La Jolla, USA.

Myoblasts from human skeletal muscle were isolated from needle biopsy samples of vastus lateralis and fused to differentiated multinucleated myotubes. Specific high-affinity insulin and insulin-like growth factor I (IGF-I) binding, glucose transporter proteins GLUT1 and GLUT4, glycogen synthase and pyruvate dehydrogenase proteins, and their specific mRNAs were identified in fused myotubes. Insulin and IGF-I stimulated 2-deoxyglucose uptake twofold with half-maximal stimulation by insulin at 0.98 +/- 0.12 nmol/l and maximal stimulation at 17.5 nmol/l. Acute insulin treatment (33 nmol/l) doubled glycogen synthase activity and glucose incorporation into glycogen while increasing pyruvate dehydrogenase approximately 30%. In cells cultured from NIDDM subjects, both basal (6.9 +/- 1.0 vs. 13.0 +/- 1.7 pmol.mg protein-1.min-1) and acute insulin-stimulated transport (13.5 +/- 2.0 vs. 22.4 +/- 1.3 pmol.mg protein-1.min-1) were significantly reduced compared with nondiabetic control subjects (both P < or = 0.005). GLUT1 protein content of total membranes from NIDDM subjects was decreased compared with control subjects, while GLUT4 levels were similar between groups. A significant correlation (r = 0.65, P < or = 0.05) was present when maximal rates of insulin-stimulated glucose transport in cell culture from subjects were compared with their corresponding in vivo glucose disposal determined by hyperinsulinemic glucose clamp. In summary, differentiated human skeletal muscle cultures exhibit biochemical and molecular features of insulin-stimulated glucose transport and intracellular enzyme activity comparable with the in vivo situation. Defective insulin-stimulated glucose transport persists in muscle cultures from NIDDM subjects and resembles the reduced insulin-mediated glucose uptake present in vivo. We conclude that this technique provides a relevant cellular model to study insulin action and glucose metabolism in normal subjects and determine the mechanisms of insulin resistance in NIDDM.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. M. Reyna, S. Ghosh, P. Tantiwong, C.S. R. Meka, P. Eagan, C. P. Jenkinson, E. Cersosimo, R. A. DeFronzo, D. K. Coletta, A. Sriwijitkamol, et al. Elevated Toll-Like Receptor 4 Expression and Signaling in Muscle From Insulin-Resistant Subjects Diabetes, October 1, 2008; 57(10): 2595 - 2602. [Abstract] [Full Text] [PDF]

				Z. Q. Wang, W. T. Cefalu, X. H. Zhang, Y. Yu, J. Qin, L. Son, P. M. Rogers, N. Mashtalir, J. R. Bordelon, J. Ye, et al. Human Adenovirus Type 36 Enhances Glucose Uptake in Diabetic and Nondiabetic Human Skeletal Muscle Cells Independent of Insulin Signaling Diabetes, July 1, 2008; 57(7): 1805 - 1813. [Abstract] [Full Text] [PDF]

				T. P. Ciaraldi, S. E. Nikoulina, R. A. Bandukwala, L. Carter, and R. R. Henry Role of Glycogen Synthase Kinase-3{alpha} in Insulin Action in Cultured Human Skeletal Muscle Cells Endocrinology, September 1, 2007; 148(9): 4393 - 4399. [Abstract] [Full Text] [PDF]

				A. J. Wensaas, A. C. Rustan, K. Lovstedt, B. Kull, S. Wikstrom, C. A. Drevon, and S. Hallen Cell-based multiwell assays for the detection of substrate accumulation and oxidation J. Lipid Res., April 1, 2007; 48(4): 961 - 967. [Abstract] [Full Text] [PDF]

				M. Gaster Metabolic flexibility is conserved in diabetic myotubes J. Lipid Res., January 1, 2007; 48(1): 207 - 217. [Abstract] [Full Text] [PDF]

				M. Pendergrass, A. Bertoldo, R. Bonadonna, G. Nucci, L. Mandarino, C. Cobelli, and R. A. DeFronzo Muscle glucose transport and phosphorylation in type 2 diabetic, obese nondiabetic, and genetically predisposed individuals Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E92 - E100. [Abstract] [Full Text] [PDF]

				H. K.R. Karlsson, M. Ahlsen, J. R. Zierath, H. Wallberg-Henriksson, and H. A. Koistinen Insulin signaling and glucose transport in skeletal muscle from first-degree relatives of type 2 diabetic patients. Diabetes, May 1, 2006; 55(5): 1283 - 1288. [Abstract] [Full Text] [PDF]

				A. Corbould, H. Zhao, S. Mirzoeva, F. Aird, and A. Dunaif Enhanced Mitogenic Signaling in Skeletal Muscle of Women With Polycystic Ovary Syndrome Diabetes, March 1, 2006; 55(3): 751 - 759. [Abstract] [Full Text] [PDF]

				V. Aas, M. H. Rokling-Andersen, E. T. Kase, G. H. Thoresen, and A. C. Rustan Eicosapentaenoic acid (20:5 n-3) increases fatty acid and glucose uptake in cultured human skeletal muscle cells J. Lipid Res., February 1, 2006; 47(2): 366 - 374. [Abstract] [Full Text] [PDF]

				T. P. Ciaraldi, S. A. Phillips, L. Carter, V. Aroda, S. Mudaliar, and R. R. Henry Effects of the Rapid-Acting Insulin Analog Glulisine on Cultured Human Skeletal Muscle Cells: Comparisons with Insulin and Insulin-Like Growth Factor I J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5551 - 5558. [Abstract] [Full Text] [PDF]

				B.-S. Cha, T. P. Ciaraldi, K.-S. Park, L. Carter, S. R. Mudaliar, and R. R. Henry Impaired fatty acid metabolism in type 2 diabetic skeletal muscle cells is reversed by PPAR{gamma} agonists Am J Physiol Endocrinol Metab, July 1, 2005; 289(1): E151 - E159. [Abstract] [Full Text] [PDF]

				A. Corbould, Y.-B. Kim, J. F. Youngren, C. Pender, B. B. Kahn, A. Lee, and A. Dunaif Insulin resistance in the skeletal muscle of women with PCOS involves intrinsic and acquired defects in insulin signaling Am J Physiol Endocrinol Metab, May 1, 2005; 288(5): E1047 - E1054. [Abstract] [Full Text] [PDF]

				T. P. Ciaraldi, S. Mudaliar, A. Barzin, J. A. Macievic, S. V. Edelman, K. S. Park, and R. R. Henry Skeletal Muscle GLUT1 Transporter Protein Expression and Basal Leg Glucose Uptake Are Reduced in Type 2 Diabetes J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 352 - 358. [Abstract] [Full Text] [PDF]

				L. Al-Khalili, A. Krook, J. R. Zierath, and G. D. Cartee Prior serum- and AICAR-induced AMPK activation in primary human myocytes does not lead to subsequent increase in insulin-stimulated glucose uptake Am J Physiol Endocrinol Metab, September 1, 2004; 287(3): E553 - E557. [Abstract] [Full Text] [PDF]

				E. A. McIntyre, R. Halse, S. J. Yeaman, and M. Walker Cultured Muscle Cells from Insulin-Resistant Type 2 Diabetes Patients Have Impaired Insulin, but Normal 5-Amino-4-Imidazolecarboxamide Riboside-Stimulated, Glucose Uptake J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3440 - 3448. [Abstract] [Full Text] [PDF]

				M. Gaster, A. C. Rustan, V. Aas, and H. Beck-Nielsen Reduced Lipid Oxidation in Skeletal Muscle From Type 2 Diabetic Subjects May Be of Genetic Origin: Evidence From Cultured Myotubes Diabetes, March 1, 2004; 53(3): 542 - 548. [Abstract] [Full Text] [PDF]

				Y. Gosmain, E. Lefai, S. Ryser, M. Roques, and H. Vidal Sterol Regulatory Element-Binding Protein-1 Mediates the Effect of Insulin on Hexokinase II Gene Expression in Human Muscle Cells Diabetes, February 1, 2004; 53(2): 321 - 329. [Abstract] [Full Text]

				H. M. Wilmsen, T. P. Ciaraldi, L. Carter, N. Reehman, S. R. Mudaliar, and R. R. Henry Thiazolidinediones upregulate impaired fatty acid uptake in skeletal muscle of type 2 diabetic subjects Am J Physiol Endocrinol Metab, August 1, 2003; 285(2): E354 - E362. [Abstract] [Full Text] [PDF]

				K. Bouzakri, M. Roques, P. Gual, S. Espinosa, F. Guebre-Egziabher, J.-P. Riou, M. Laville, Y. Le Marchand-Brustel, J.-F. Tanti, and H. Vidal Reduced Activation of Phosphatidylinositol-3 Kinase and Increased Serine 636 Phosphorylation of Insulin Receptor Substrate-1 in Primary Culture of Skeletal Muscle Cells From Patients With Type 2 Diabetes Diabetes, June 1, 2003; 52(6): 1319 - 1325. [Abstract] [Full Text] [PDF]

				M. G. Clark, M. G. Wallis, E. J. Barrett, M. A. Vincent, S. M. Richards, L. H. Clerk, and S. Rattigan Blood flow and muscle metabolism: a focus on insulin action Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E241 - E258. [Abstract] [Full Text] [PDF]

				A. Haupt, C. Kausch, D. Dahl, O. Bachmann, M. Stumvoll, H.-U. Haring, and S. Matthaei Effect of Glimepiride on Insulin-Stimulated Glycogen Synthesis in Cultured Human Skeletal Muscle Cells: A comparison to glibenclamide Diabetes Care, December 1, 2002; 25(12): 2129 - 2132. [Abstract] [Full Text] [PDF]

				S. E. Nikoulina, T. P. Ciaraldi, S. Mudaliar, L. Carter, K. Johnson, and R. R. Henry Inhibition of Glycogen Synthase Kinase 3 Improves Insulin Action and Glucose Metabolism in Human Skeletal Muscle Diabetes, July 1, 2002; 51(7): 2190 - 2198. [Abstract] [Full Text] [PDF]

				M. Gaster, I. Petersen, K. Hojlund, P. Poulsen, and H. Beck-Nielsen The Diabetic Phenotype Is Conserved in Myotubes Established From Diabetic Subjects: Evidence for Primary Defects in Glucose Transport and Glycogen Synthase Activity Diabetes, April 1, 2002; 51(4): 921 - 927. [Abstract] [Full Text] [PDF]

				P. Vollenweider, B. Menard, and P. Nicod Insulin Resistance, Defective Insulin Receptor Substrate 2--Associated Phosphatidylinositol-3' Kinase Activation, and Impaired Atypical Protein Kinase C ({zeta}/{lambda}) Activation in Myotubes From Obese Patients With Impaired Glucose Tolerance Diabetes, April 1, 2002; 51(4): 1052 - 1059. [Abstract] [Full Text] [PDF]

				H. G. Wahl, C. Kausch, F. Machicao, K. Rett, M. Stumvoll, and H.-U. Haring Troglitazone Downregulates {Delta}-6 Desaturase Gene Expression in Human Skeletal Muscle Cell Cultures Diabetes, April 1, 2002; 51(4): 1060 - 1065. [Abstract] [Full Text] [PDF]

				C. B. Whorwood, S. J. Donovan, D. Flanagan, D. I.W. Phillips, and C. D. Byrne Increased Glucocorticoid Receptor Expression in Human Skeletal Muscle Cells May Contribute to the Pathogenesis of the Metabolic Syndrome Diabetes, April 1, 2002; 51(4): 1066 - 1075. [Abstract] [Full Text] [PDF]

				S. E. Nikoulina, T. P. Ciaraldi, L. Carter, S. Mudaliar, K. S. Park, and R. R. Henry Impaired Muscle Glycogen Synthase in Type 2 Diabetes Is Associated with Diminished Phosphatidylinositol 3-Kinase Activation J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4307 - 4314. [Abstract] [Full Text] [PDF]

				L. M. Perriott, T. Kono, R. R. Whitesell, S. M. Knobel, D. W. Piston, D. K. Granner, A. C. Powers, and J. M. May Glucose uptake and metabolism by cultured human skeletal muscle cells: rate-limiting steps Am J Physiol Endocrinol Metab, July 1, 2001; 281(1): E72 - E80. [Abstract] [Full Text] [PDF]

				M. Gaster, J. Franch, P. Staehr, H. Beck-Nielsen, T. Smith, and H. D. Schroder Induction of GLUT-1 protein in adult human skeletal muscle fibers Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1191 - E1195. [Abstract] [Full Text] [PDF]

				M. Gaster, A. Handberg, H. Beck-Nielsen, and H. D. Schroder Glucose transporter expression in human skeletal muscle fibers Am J Physiol Endocrinol Metab, September 1, 2000; 279(3): E529 - E538. [Abstract] [Full Text] [PDF]

				D. M. Mott, C. Hoyt, R. Caspari, K. Stone, R. Pratley, and C. Bogardus Palmitate oxidation rate and action on glycogen synthase in myoblasts from insulin-resistant subjects Am J Physiol Endocrinol Metab, September 1, 2000; 279(3): E561 - E569. [Abstract] [Full Text] [PDF]

				C. E. Chalfant, T. P. Ciaraldi, J. E. Watson, S. Nikoulina, R. R. Henry, and D. R. Cooper Protein Kinase C{theta} Expression Is Increased upon Differentiation of Human Skeletal Muscle Cells: Dysregulation in Type 2 Diabetic Patients and a Possible Role for Protein Kinase C{theta} in Insulin-Stimulated Glycogen Synthase Activity Endocrinology, August 1, 2000; 141(8): 2773 - 2778. [Abstract] [Full Text] [PDF]

				M. Roques and H. Vidal A Phosphatidylinositol 3-Kinase/p70 Ribosomal S6 Protein Kinase Pathway Is Required for the Regulation by Insulin of the p85alpha Regulatory Subunit of Phosphatidylinositol 3-Kinase Gene Expression in Human Muscle Cells J. Biol. Chem., November 26, 1999; 274(48): 34005 - 34010. [Abstract] [Full Text] [PDF]

				C.-B. Book and A. Dunaif Selective Insulin Resistance in the Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3110 - 3116. [Abstract] [Full Text]

				T. P. Ciaraldi, L. Carter, S. Nikoulina, S. Mudaliar, D. A. McClain, and R. R. Henry Glucosamine Regulation of Glucose Metabolism in Cultured Human Skeletal Muscle Cells: Divergent Effects on Glucose Transport/Phosphorylation and Glycogen Synthase in Non-Diabetic and Type 2 Diabetic Subjects Endocrinology, September 1, 1999; 140(9): 3971 - 3980. [Abstract] [Full Text]

				D. Furling, A. Marette, and J. Puymirat Insulin-Like Growth Factor I Circumvents Defective Insulin Action in Human Myotonic Dystrophy Skeletal Muscle Cells Endocrinology, September 1, 1999; 140(9): 4244 - 4250. [Abstract] [Full Text]

				J. F. Youngren, I. D. Goldfine, and R. E. Pratley Insulin receptor autophosphorylation in cultured myoblasts correlates to glucose disposal in Pima Indians Am J Physiol Endocrinol Metab, May 1, 1999; 276(5): E990 - E994. [Abstract] [Full Text] [PDF]

				T. P. Ciaraldi, L. Carter, S. Mudaliar, P. A. Kern, and R. R. Henry Effects of Tumor Necrosis Factor-{alpha} on Glucose Metabolism in Cultured Human Muscle Cells from Nondiabetic and Type 2 Diabetic Subjects Endocrinology, December 1, 1998; 139(12): 4793 - 4800. [Abstract] [Full Text] [PDF]

				K. S. Park, T. P. Ciaraldi, K. Lindgren, L. Abrams-Carter, S. Mudaliar, S. E. Nikoulina, S. R. Tufari, J. H. Veerkamp, A. Vidal-Puig, and R. R. Henry Troglitazone Effects on Gene Expression in Human Skeletal Muscle of Type II Diabetes Involve Up-Regulation of Peroxisome Proliferator-Activated Receptor-{gamma} J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2830 - 2835. [Abstract] [Full Text]

				K. S. Park, T. P. Ciaraldi, L. Abrams-Carter, S. Mudaliar, S. E. Nikoulina, and R. R. Henry Troglitazone Regulation of Glucose Metabolism in Human Skeletal Muscle Cultures from Obese Type II Diabetic Subjects J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1636 - 1643. [Abstract] [Full Text]

				P. A. Kern Potential Role of TNFalpha and Lipoprotein Lipase as Candidate Genes for Obesity J. Nutr., September 1, 1997; 127(9): 1917 - 1917. [Abstract] [Full Text]

				H. Esterbauer, H. Oberkofler, F. Krempler, A. D. Strosberg, and W. Patsch The Uncoupling Protein-3 Gene Is Transcribed from Tissue-specific Promoters in Humans but Not in Rodents J. Biol. Chem., November 10, 2000; 275(46): 36394 - 36399. [Abstract] [Full Text] [PDF]