Diabetes, Vol 46, Issue 2 215-223, Copyright © 1997 by American Diabetes Association

ARTICLES

High-fat feeding impairs insulin-stimulated GLUT4 recruitment via an early insulin-signaling defect

JR Zierath, KL Houseknecht, L Gnudi and BB Kahn
Department of Medicine at Harvard Medical School and Beth Israel Hospital, Boston, Massachusetts, USA. jrz@klinfys.ks.se

Glucose transport in skeletal muscle can be mediated by two separate pathways, one stimulated by insulin and the other by muscle contraction. High-fat feeding impairs glucose transport in muscle, but the mechanism remains unclear. FVB mice (3 weeks old) were fed a high-fat diet (55% fat, 24% carbohydrate, 21% protein) or standard chow for 3-4 weeks or 8 weeks. Insulin-stimulated glucose transport, assessed with either 2-deoxyglucose or 3-O-methylglucose was decreased 35-45% (P < 0.001) in isolated soleus muscle, regardless of diet duration. Similarly, glucose transport stimulated by okadaic acid, a serine/threonine phosphatase inhibitor, was also 45% lower with high-fat feeding, but the glucose transport response to hypoxia or N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) (which are stimulators of the "contraction pathway") was intact. Hexokinase I, II, and total activity were normal in soleus muscle from high-fat-fed mice. GLUT4 expression in soleus muscle from the high-fat-fed mice was also normal, but the insulin-stimulated cell surface recruitment of GLUT4 assessed by exofacial photolabeling with [3H]-ATB bis-mannose was reduced by 50% (P < 0.001). Insulin-receptor substrate 1 (IRS-1) associated phosphatidylinositol (PI) 3-kinase activity stimulated by insulin was also reduced by 36% (P < 0.001), and expression of p85 and p110b subunits of PI 3-kinase was normal. In conclusion, high-fat feeding selectively impairs insulin-stimulated, but not contraction-pathway-mediated, glucose transport by reducing GLUT4 translocation to the plasma membrane. This appears to result from an acquired defect in insulin activation of PI 3-kinase. Since effects of okadaic acid on glucose transport are independent of PI 3-kinase, a second signaling defect may also be induced.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. P.M. M. Lauritzen, T. Ploug, H. Ai, M. Donsmark, C. Prats, and H. Galbo Denervation and High-Fat Diet Reduce Insulin Signaling in T-Tubules in Skeletal Muscle of Living Mice Diabetes, January 1, 2008; 57(1): 13 - 23. [Abstract] [Full Text] [PDF]

				R. Buettner, I. Ottinger, C. Gerhardt-Salbert, C. E. Wrede, J. Scholmerich, and L. C. Bollheimer Antisense oligonucleotides against the lipid phosphatase SHIP2 improve muscle insulin sensitivity in a dietary rat model of the metabolic syndrome Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1871 - E1878. [Abstract] [Full Text] [PDF]

				Y. I. Kim, F. N. Lee, W. S. Choi, S. Lee, and J. H. Youn Insulin Regulation of Skeletal Muscle PDK4 mRNA Expression Is Impaired in Acute Insulin-Resistant States. Diabetes, August 1, 2006; 55(8): 2311 - 2317. [Abstract] [Full Text] [PDF]

				K. H. Treiber, D. S. Kronfeld, and R. J. Geor Insulin Resistance in Equids: Possible Role in Laminitis J. Nutr., July 1, 2006; 136(7): 2094S - 2098S. [Abstract] [Full Text] [PDF]

				P. Kishore, J. Tonelli, S. Koppaka, C. Fratila, A. Bose, D.-E. Lee, K. Reddy, and M. Hawkins Time-Dependent Effects of Free Fatty Acids on Glucose Effectiveness in Type 2 Diabetes Diabetes, June 1, 2006; 55(6): 1761 - 1768. [Abstract] [Full Text] [PDF]

				K. Togawa, M. Moritani, H. Yaguchi, and M. Itakura Multidimensional genome scans identify the combinations of genetic loci linked to diabetes-related phenotypes in mice Hum. Mol. Genet., January 1, 2006; 15(1): 113 - 128. [Abstract] [Full Text] [PDF]

				I. Talukdar, W. Szeszel-Fedorowicz, and L. M. Salati Arachidonic Acid Inhibits the Insulin Induction of Glucose-6-phosphate Dehydrogenase via p38 MAP Kinase J. Biol. Chem., December 9, 2005; 280(49): 40660 - 40667. [Abstract] [Full Text] [PDF]

				E. Isganaitis and R. H. Lustig Fast Food, Central Nervous System Insulin Resistance, and Obesity Arterioscler. Thromb. Vasc. Biol., December 1, 2005; 25(12): 2451 - 2462. [Abstract] [Full Text] [PDF]

				N. Wijesekara, D. Konrad, M. Eweida, C. Jefferies, N. Liadis, A. Giacca, M. Crackower, A. Suzuki, T. W. Mak, C. R. Kahn, et al. Muscle-Specific Pten Deletion Protects against Insulin Resistance and Diabetes Mol. Cell. Biol., February 1, 2005; 25(3): 1135 - 1145. [Abstract] [Full Text] [PDF]

				B. R. Barnes, S. Marklund, T. L. Steiler, M. Walter, G. Hjalm,, V. Amarger, M. Mahlapuu, Y. Leng, C. Johansson, D. Galuska, et al. The 5'-AMP-activated Protein Kinase {gamma}3 Isoform Has a Key Role in Carbohydrate and Lipid Metabolism in Glycolytic Skeletal Muscle J. Biol. Chem., September 10, 2004; 279(37): 38441 - 38447. [Abstract] [Full Text] [PDF]

				J. P. Stoehr, J. E. Byers, S. M. Clee, H. Lan, I. V. Boronenkov, K. L. Schueler, B. S. Yandell, and A. D. Attie Identification of Major Quantitative Trait Loci Controlling Body Weight Variation in ob/ob Mice Diabetes, January 1, 2004; 53(1): 245 - 249. [Abstract] [Full Text] [PDF]

				J. W. Ryder, R. Bassel-Duby, E. N. Olson, and J. R. Zierath Skeletal Muscle Reprogramming by Activation of Calcineurin Improves Insulin Action on Metabolic Pathways J. Biol. Chem., November 7, 2003; 278(45): 44298 - 44304. [Abstract] [Full Text] [PDF]

				M. Hawkins, J. Tonelli, P. Kishore, D. Stein, E. Ragucci, A. Gitig, and K. Reddy Contribution of Elevated Free Fatty Acid Levels to the Lack of Glucose Effectiveness in Type 2 Diabetes Diabetes, November 1, 2003; 52(11): 2748 - 2758. [Abstract] [Full Text] [PDF]

				I. R. Schlaepfer, L. K. Pulawa, L. D. M. C-B. Ferreira, D. E. James, W. H. Capell, and R. H. Eckel Increased expression of the SNARE accessory protein Munc18c in lipid-mediated insulin resistance J. Lipid Res., June 1, 2003; 44(6): 1174 - 1181. [Abstract] [Full Text] [PDF]

				W. Niu, C. Huang, Z. Nawaz, M. Levy, R. Somwar, D. Li, P. J. Bilan, and A. Klip Maturation of the Regulation of GLUT4 Activity by p38 MAPK during L6 Cell Myogenesis J. Biol. Chem., May 9, 2003; 278(20): 17953 - 17962. [Abstract] [Full Text] [PDF]

				J. He, M. Thamotharan, and S. U. Devaskar Insulin-induced translocation of facilitative glucose transporters in fetal/neonatal rat skeletal muscle Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R1138 - R1146. [Abstract] [Full Text] [PDF]

				Y. Kanoh, M. P. Sajan, G. Bandyopadhyay, A. Miura, M. L. Standaert, and R. V. Farese Defective Activation of Atypical Protein Kinase C {zeta} and {lambda} by Insulin and Phosphatidylinositol-3,4,5-(PO4)3 in Skeletal Muscle of Rats Following High-Fat Feeding and Streptozotocin-Induced Diabetes Endocrinology, March 1, 2003; 144(3): 947 - 954. [Abstract] [Full Text] [PDF]

				F. Tremblay, C. Lavigne, H. Jacques, and A. Marette Dietary Cod Protein Restores Insulin-Induced Activation of Phosphatidylinositol 3-Kinase/Akt and GLUT4 Translocation to the T-Tubules in Skeletal Muscle of High-Fat-Fed Obese Rats Diabetes, January 1, 2003; 52(1): 29 - 37. [Abstract] [Full Text] [PDF]

				R. Somwar, S. Koterski, G. Sweeney, R. Sciotti, S. Djuric, C. Berg, J. Trevillyan, P. E. Scherer, C. M. Rondinone, and A. Klip A Dominant-negative p38 MAPK Mutant and Novel Selective Inhibitors of p38 MAPK Reduce Insulin-stimulated Glucose Uptake in 3T3-L1 Adipocytes without Affecting GLUT4 Translocation J. Biol. Chem., December 20, 2002; 277(52): 50386 - 50395. [Abstract] [Full Text] [PDF]

				B. R. Barnes, J. W. Ryder, T. L. Steiler, L. G.D. Fryer, D. Carling, and J. R. Zierath Isoform-Specific Regulation of 5' AMP-Activated Protein Kinase in Skeletal Muscle From Obese Zucker (fa/fa) Rats in Response to Contraction Diabetes, September 1, 2002; 51(9): 2703 - 2708. [Abstract] [Full Text] [PDF]

				E. Tomas, A. Zorzano, and N. B. Ruderman Exercise Effects on Muscle Insulin Signaling and Action: Exercise and insulin signaling: a historical perspective J Appl Physiol, August 1, 2002; 93(2): 765 - 772. [Abstract] [Full Text] [PDF]

				A. Hevener, D. Reichart, A. Janez, and J. Olefsky Female Rats Do Not Exhibit Free Fatty Acid-Induced Insulin Resistance Diabetes, June 1, 2002; 51(6): 1907 - 1912. [Abstract] [Full Text] [PDF]

				B. D. Hegarty, G. J. Cooney, E. W. Kraegen, and S. M. Furler Increased Efficiency of Fatty Acid Uptake Contributes to Lipid Accumulation in Skeletal Muscle of High Fat-Fed Insulin-Resistant Rats Diabetes, May 1, 2002; 51(5): 1477 - 1484. [Abstract] [Full Text] [PDF]

				C. S. Choi, F. N. Lee, A. A. McDonough, and J. H. Youn Independent Regulation of In Vivo Insulin Action on Glucose Versus K+ Uptake by Dietary Fat and K+ Content Diabetes, April 1, 2002; 51(4): 915 - 920. [Abstract] [Full Text] [PDF]

				P. Shah, A. Vella, A. Basu, R. Basu, A. Adkins, W. F. Schwenk, C. M. Johnson, K. S. Nair, M. D. Jensen, and R. A. Rizza Effects of Free Fatty Acids and Glycerol on Splanchnic Glucose Metabolism and Insulin Extraction in Nondiabetic Humans Diabetes, February 1, 2002; 51(2): 301 - 310. [Abstract] [Full Text] [PDF]

				J. F. Youngren, J. Paik, and R. J. Barnard Impaired insulin-receptor autophosphorylation is an early defect in fat-fed, insulin-resistant rats J Appl Physiol, November 1, 2001; 91(5): 2240 - 2247. [Abstract] [Full Text] [PDF]

				M. Agote, L. Goya, S. Ramos, C. Alvarez, M. L. Gavete, A. M. Pascual-Leone, and F. Escriva Glucose uptake and glucose transporter proteins in skeletal muscle from undernourished rats Am J Physiol Endocrinol Metab, November 1, 2001; 281(5): E1101 - E1109. [Abstract] [Full Text] [PDF]

				F. Tremblay, C. Lavigne, H. Jacques, and A. Marette Defective Insulin-Induced GLUT4 Translocation in Skeletal Muscle of High Fat-Fed Rats Is Associated With Alterations in Both Akt/Protein Kinase B and Atypical Protein Kinase C ({zeta}/{lambda}) Activities Diabetes, August 1, 2001; 50(8): 1901 - 1910. [Abstract] [Full Text] [PDF]

				J.W. Ryder, C.P. Portocarrero, X.M. Song, L. Cui, M. Yu, T. Combatsiaris, D. Galuska, D.E. Bauman, D.M. Barbano, M.J. Charron, et al. Isomer-Specific Antidiabetic Properties of Conjugated Linoleic Acid: Improved Glucose Tolerance, Skeletal Muscle Insulin Action, and UCP-2 Gene Expression Diabetes, May 1, 2001; 50(5): 1149 - 1157. [Abstract] [Full Text]

				C. Yang, S. Mora, J. W. Ryder, K. J. Coker, P. Hansen, L.-A. Allen, and J. E. Pessin VAMP3 Null Mice Display Normal Constitutive, Insulin- and Exercise-Regulated Vesicle Trafficking Mol. Cell. Biol., March 1, 2001; 21(5): 1573 - 1580. [Abstract] [Full Text]

				J.-M. Ye, P. J. Doyle, M. A. Iglesias, D. G. Watson, G. J. Cooney, and E. W. Kraegen Peroxisome Proliferator--Activated Receptor (PPAR)-{alpha} Activation Lowers Muscle Lipids and Improves Insulin Sensitivity in High Fat--Fed Rats: Comparison With PPAR-{gamma} Activation Diabetes, February 1, 2001; 50(2): 411 - 417. [Abstract] [Full Text]

				R. L. Dobbins, L. S. Szczepaniak, B. Bentley, V. Esser, J. Myhill, and J. D. McGarry Prolonged Inhibition of Muscle Carnitine Palmitoyltransferase-1 Promotes Intramyocellular Lipid Accumulation and Insulin Resistance in Rats Diabetes, January 1, 2001; 50(1): 123 - 130. [Abstract] [Full Text]

				G. R. Steinberg and D. J. Dyck Development of leptin resistance in rat soleus muscle in response to high-fat diets Am J Physiol Endocrinol Metab, December 1, 2000; 279(6): E1374 - E1382. [Abstract] [Full Text] [PDF]

				J.-Y. Kim, L. A. Nolte, P. A. Hansen, D.-H. Han, K. Ferguson, P. A. Thompson, and J. O. Holloszy High-fat diet-induced muscle insulin resistance: relationship to visceral fat mass Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2000; 279(6): R2057 - R2065. [Abstract] [Full Text] [PDF]

				A. E. Halseth, D. P. Bracy, and D. H. Wasserman Limitations to basal and insulin-stimulated skeletal muscle glucose uptake in the high-fat-fed rat Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1064 - E1071. [Abstract] [Full Text] [PDF]

				K. S. Bell, C. Schmitz-Peiffer, M. Lim-Fraser, T. J. Biden, G. J. Cooney, and E. W. Kraegen Acute reversal of lipid-induced muscle insulin resistance is associated with rapid alteration in PKC-theta localization Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1196 - E1201. [Abstract] [Full Text] [PDF]

				A. L. Thompson, M. Y.-C. Lim-Fraser, E. W. Kraegen, and G. J. Cooney Effects of individual fatty acids on glucose uptake and glycogen synthesis in soleus muscle in vitro Am J Physiol Endocrinol Metab, September 1, 2000; 279(3): E577 - E584. [Abstract] [Full Text] [PDF]

				C.-H. Kim, J. H. Youn, J.-Y. Park, S. K. Hong, K. S. Park, S. W. Park, K. I. Suh, and K.-U. Lee Effects of high-fat diet and exercise training on intracellular glucose metabolism in rats Am J Physiol Endocrinol Metab, June 1, 2000; 278(6): E977 - E984. [Abstract] [Full Text] [PDF]

				R. Buettner, C. B. Newgard, C. J. Rhodes, and R. M. O'Doherty Correction of diet-induced hyperglycemia, hyperinsulinemia, and skeletal muscle insulin resistance by moderate hyperleptinemia Am J Physiol Endocrinol Metab, March 1, 2000; 278(3): E563 - E569. [Abstract] [Full Text] [PDF]

				P. R. Shepherd and B. B. Kahn Glucose Transporters and Insulin Action -- Implications for Insulin Resistance and Diabetes Mellitus N. Engl. J. Med., July 22, 1999; 341(4): 248 - 257. [Full Text] [PDF]

				A. M. Lombardi, R. Fabris, F. Bassetto, R. Serra, A. Leturque, G. Federspil, J. Girard, and R. Vettor Hyperlactatemia reduces muscle glucose uptake and GLUT-4 mRNA while increasing (E1alpha )PDH gene expression in rat Am J Physiol Endocrinol Metab, May 1, 1999; 276(5): E922 - E929. [Abstract] [Full Text] [PDF]

				J.-Y. Kim, L. A. Nolte, P. A. Hansen, D.-H. Han, K. Kawanaka, and J. O. Holloszy Insulin resistance of muscle glucose transport in male and female rats fed a high-sucrose diet Am J Physiol Regulatory Integrative Comp Physiol, March 1, 1999; 276(3): R665 - R672. [Abstract] [Full Text] [PDF]

				B. A. Marshall, P. A. Hansen, N. J. Ensor, M. A. Ogden, and M. Mueckler GLUT-1 or GLUT-4 transgenes in obese mice improve glucose tolerance but do not prevent insulin resistance Am J Physiol Endocrinol Metab, February 1, 1999; 276(2): E390 - E400. [Abstract] [Full Text] [PDF]

				D. J. Dean, J. T. Brozinick Jr., S. W. Cushman, and G. D. Cartee Calorie restriction increases cell surface GLUT-4 in insulin-stimulated skeletal muscle Am J Physiol Endocrinol Metab, December 1, 1998; 275(6): E957 - E964. [Abstract] [Full Text] [PDF]

				M. Anai, H. Ono, M. Funaki, Y. Fukushima, K. Inukai, T. Ogihara, H. Sakoda, Y. Onishi, Y. Yazaki, M. Kikuchi, et al. Different Subcellular Distribution and Regulation of Expression of Insulin Receptor Substrate (IRS)-3 from Those of IRS-1 and IRS-2 J. Biol. Chem., November 6, 1998; 273(45): 29686 - 29692. [Abstract] [Full Text] [PDF]

				P. A. Hansen, D. H. Han, B. A. Marshall, L. A. Nolte, M. M. Chen, M. Mueckler, and J. O. Holloszy A High Fat Diet Impairs Stimulation of Glucose Transport in Muscle. FUNCTIONAL EVALUATION OF POTENTIAL MECHANISMS J. Biol. Chem., October 2, 1998; 273(40): 26157 - 26163. [Abstract] [Full Text] [PDF]

				U. Widegren, X. J. Jiang, A. Krook, A. V. Chibalin, M. Björnholm, M. Tally, R. A. Roth, J. Henriksson, H. Wallberg-henriksson, and J. R. Zierath Divergent effects of exercise on metabolic and mitogenic signaling pathways in human skeletal muscle FASEB J, October 1, 1998; 12(13): 1379 - 1389. [Abstract] [Full Text]

				J. J. Wilkes, A. Bonen, and R. C. Bell A modified high-fat diet induces insulin resistance in rat skeletal muscle but not adipocytes Am J Physiol Endocrinol Metab, October 1, 1998; 275(4): E679 - E686. [Abstract] [Full Text] [PDF]

				J. R. Zierath, T.-S. Tsao, A. E. Stenbit, J. W. Ryder, D. Galuska, and M. J. Charron Restoration of Hypoxia-stimulated Glucose Uptake in GLUT4-deficient Muscles by Muscle-specific GLUT4 Transgenic Complementation J. Biol. Chem., August 14, 1998; 273(33): 20910 - 20915. [Abstract] [Full Text] [PDF]

				L. Strommer, J. Permert, U. Arnelo, C. Koehler, B. Isaksson, J. Larsson, I. Lundkvist, M. Bjornholm, Y. Kawano, H. Wallberg-Henriksson, et al. Skeletal muscle insulin resistance after trauma: insulin signaling and glucose transport Am J Physiol Endocrinol Metab, August 1, 1998; 275(2): E351 - E358. [Abstract] [Full Text] [PDF]

				T. Ranheim, C. Dumke, K. L. Schueler, G. D. Cartee, and A. D. Attie Interaction Between BTBR and C57BL/6J Genomes Produces an Insulin Resistance Syndrome in (BTBR x C57BL/6J) F1 Mice Arterioscler. Thromb. Vasc. Biol., November 1, 1997; 17(11): 3286 - 3293. [Abstract] [Full Text]

				M. Van Epps-Fung, J. Williford, A. Wells, and R. W. Hardy Fatty Acid-Induced Insulin Resistance in Adipocytes Endocrinology, October 1, 1997; 138(10): 4338 - 4345. [Abstract] [Full Text] [PDF]

				F. Picard, A. Boivin, J. Lalonde, and Y. Deshaies Resistance of adipose tissue lipoprotein lipase to insulin action in rats fed an obesity-promoting diet Am J Physiol Endocrinol Metab, February 1, 2002; 282(2): E412 - E418. [Abstract] [Full Text] [PDF]

				M. Taouis, C. Dagou, C. Ster, G. Durand, M. Pinault, and J. Delarue N-3 Polyunsaturated fatty acids prevent the defect of insulin receptor signaling in muscle Am J Physiol Endocrinol Metab, March 1, 2002; 282(3): E664 - E671. [Abstract] [Full Text] [PDF]