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Regulation of glucose transport by the AMP-activated protein kinase

Published online by Cambridge University Press:  05 March 2007

Nobuharu Fujii
Affiliation:
The Research Division, Joslin Diabetes Center and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA
William G. Aschenbach
Affiliation:
The Research Division, Joslin Diabetes Center and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA
Nicolas Musi
Affiliation:
The Research Division, Joslin Diabetes Center and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA
Michael F. Hirshman
Affiliation:
The Research Division, Joslin Diabetes Center and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA
Laurie J. Goodyear
Affiliation:
The Research Division, Joslin Diabetes Center and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA
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Abstract

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The AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is activated during exercise and muscle contraction as a result of acute decreases in ATP:AMP and phosphocreatine:creatine. Physical exercise increases muscle glucose uptake, enhances insulin sensitivity and leads to fatty acid oxidation in muscle. An important issue in muscle biology is to understand whether AMPK plays a role in mediating these metabolic processes. AMPK has also been implicated in regulating gene transcription and, therefore, may function in some of the cellular adaptations to training exercise. Recent studies have shown that the magnitude of AMPK activation and associated metabolic responses are affected by factors such as glycogen content, exercise training and fibre type. There have also been conflicting reports as to whether AMPK activity is necessary for contraction-stimulated glucose transport. Thus, during the next several years considerably more research will be necessary in order to fully understand the role of AMPK in regulating glucose transport in skeletal muscle.

Type
Symposium 1: Exercise signalling pathways controlling fuel oxidation during and after exercise
Copyright
Copyright © The Nutrition Society 2004

References

Ai, H, Ihlemann, J, Hellsten, Y, Lauritzen, HP, Hardie, DG, Galbo, H & Ploug, T (2002) Effect of fiber type and nutritional state on AICAR- and contraction-stimulated glucose transport in rat muscle. American Journal of Physiology 282, E1291E1300.Google Scholar
Balon, TW (1999) Integrative biology of nitric oxide and exercise. Exercise and Sport Sciences Review 27, 219253.Google Scholar
Barnes, BR, Ryder, JW, Steiler, TL, Fryer, LG, Carling, D & Zierath, JR (2002) Isoform-specific regulation of 5' AMP-activated protein kinase in skeletal muscle from obese Zucker (fa/fa) rats in response to contraction. Diabetes 51, 27032708.Google Scholar
Bergeron, R, Russell, RR III, Young, LH, Ren, JM, Marcucci, M, Lee, A & Shulman, GI (1999) Effect of AMPK activation on muscle glucose metabolism in conscious rats. American Journal of Physiology 276, E938E944.Google Scholar
Chen, HC, Bandyopadhyay, G, Sajan, MP, Kanoh, Y, Standaert, M, Farese, RV Jr & Farese, RV (2002) Activation of the ERK pathway and atypical protein kinase C isoforms in exercise- and aminoimidazole-4-carboxamide-1-beta-D-riboside (AICAR)-stimulated glucose transport. Journal of Biological Chemistry 277, 2355423562.Google Scholar
Chen, Z, Heierhorst, J, Mann, RJ, Mitchelhill, KI, Michell, BJ, Witters, LA, Lynch, GS, Kemp, BE & Stapleton, D (1999 a) Expression of the AMP-activated protein kinase beta1 and beta2 subunits in skeletal muscle. FEBS Letters 460, 343348.CrossRefGoogle ScholarPubMed
Chen, ZP, McConell, GK, Michell, BJ, Snow, RJ, Canny, BJ & Kemp, BE (2000) AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation. American Journal of Physiology 279, E1202E1206.Google ScholarPubMed
Chen, ZP, Mitchelhill, KI, Michell, BJ, Stapleton, D, Rodriguez-Crespo, I, Witters, LA, Power, DA, Ortiz de Montellano, PR & Kemp, BE (1999 b) AMP-activated protein kinase phosphorylation of endothelial NO synthase. FEBS Letters 443, 285289.Google Scholar
Cheung, PC, Salt, IP, Davies, SP, Hardie, DG & Carling, D (2000) Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding. Biochemical Journal 346, 659669.Google Scholar
Durante, PE, Mustard, KJ, Park, SH, Winder, WW & Hardie, DG (2002) Effects of endurance training on activity and expression of AMP-activated protein kinase isoforms in rat muscles. American Journal of Physiology 283, E178E186.Google ScholarPubMed
Etgen, GJ Jr, Fryburg, DA & Gibbs, EM (1997) Nitric oxide stimulates skeletal muscle glucose transport through a calcium/contraction- and phosphatidylinositol-3-kinase-independent pathway. Diabetes 46, 19151919.Google Scholar
Fryer, LG, Foufelle, F, Barnes, K, Baldwin, SA, Woods, A & Carling, D (2002) Characterization of the role of the AMP-activated protein kinase in the stimulation of glucose transport in skeletal muscle cells. Biochemical Journal 363, 167174.CrossRefGoogle ScholarPubMed
Fryer, LG, Hajduch, E, Rencurel, F, Salt, IP, Hundal, HS, Hardie, DG & Carling, D (2000) Activation of glucose transport by AMP-activated protein kinase via stimulation of nitric oxide synthase. Diabetes 49, 19781985.Google Scholar
Fujii, N, Hayashi, T, Hirshman, MF, Smith, JT, Habinowski, SA, Kaijser, L, Mu, J, Ljungqvist, O, Birnbaum, MJ, Witters, LA, Thorell, A & Goodyear, LJ (2000) Exercise induces isoform-specific increase in 5'AMP-activated protein kinase activity in human skeletal muscle. Biochemical and Biophysical Research Communications 273, 11501155.CrossRefGoogle ScholarPubMed
Hardie, DG, Carling, D & Carlson, M (1998) The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell. Annual Review of Biochemistry 67, 821855.Google Scholar
Hardie, DG & Hawley, SA (2001) AMP-activated protein kinase: the energy charge hypothesis revisited. Bioessays 23, 11121119.CrossRefGoogle ScholarPubMed
Hayashi, T, Hirshman, MF, Dufresne, SD & Goodyear, LJ (1999) Skeletal muscle contractile activity in vitro stimulates mitogen-activated protein kinase signaling. American Journal of Physiology 277, C701C707.Google Scholar
Hayashi, T, Hirshman, MF, Fujii, N, Habinowski, SA, Witters, LA & Goodyear, LJ (2000) Metabolic stress and altered glucose transport: Activation of AMP-activated protein kinase as a unifying coupling mechanism. Diabetes 49, 527531.CrossRefGoogle ScholarPubMed
Hayashi, T, Hirshman, MF, Kurth, EJ, Winder, WW & Goodyear, LJ (1998) Evidence for 5' AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes 47, 13691373.Google Scholar
Henriksen, EJ, Rodnick, KJ & Holloszy, JO (1989 a) Activation of glucose transport in skeletal muscle by phospholipase C and phorbol ester. Evaluation of the regulatory roles of protein kinase C and calcium. Journal of Biological Chemistry 264, 2153621543.CrossRefGoogle ScholarPubMed
Henriksen, EJ, Sleeper, MD, Zierath, JR & Holloszy, JO (1989 b) Polymyxin B inhibits stimulation of glucose transport in muscle by hypoxia or contractions. American Journal of Physiology 256, E662E667.Google Scholar
Higaki, Y, Hirshman, MF, Fujii, N & Goodyear, LJ (2001) Nitric oxide increases glucose uptake through a mechanism that is distinct from the insulin and contraction pathways in rat skeletal muscle. Diabetes 50, 241247.CrossRefGoogle ScholarPubMed
Hutber, CA, Hardie, DG & Winder, WW (1997) Electrical stimulation inactivates muscle acetyl-CoA carboxylase and increases AMP-activated protein kinase. American Journal of Physiology 272, E262E266.Google Scholar
Ihlemann, J, Galbo, H & Ploug, T (1999 a) Calphostin C is an inhibitor of contraction, but not insulin-stimulated glucose transport, in skeletal muscle. Acta Physiologica Scandinavica 167, 6975.Google Scholar
Ihlemann, J, Ploug, T, Hellsten, Y & Galbo, H (1999 b) Effect of tension on contraction-induced glucose transport in rat skeletal muscle. American Journal of Physiology 277, E208E214.Google Scholar
Jorgensen, SB, Viollet, B, Andreelli, F, Frosig, C, Birk, JB, Schjerling, P, Vaulont, S, Richter, EA & Wojtaszewski, JF (2003) Knockout of the α2 but not α1 5'-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside but not contraction-induced glucose uptake in skeletal muscle. Journal of Biological Chemistry 279, 10701079.CrossRefGoogle Scholar
Kawanaka, K, Nolte, LA, Han, DH, Hansen, PA & Holloszy, JO (2000) Mechanisms underlying impaired GLUT-4 translocation in glycogen-supercompensated muscles of exercised rats. American Journal of Physiology 279, E1311E1318.Google Scholar
Kemp, BE, Mitchelhill, KI, Stapleton, D, Michell, BJ, Chen, ZP & Witters, LA (1999) Dealing with energy demand: the AMP-activated protein kinase. Trends in Biochemical Sciences 24, 2225.CrossRefGoogle ScholarPubMed
Kurth-Kraczek, EJ, Hirshman, MF, Goodyear, LJ & Winder, WW (1999) 5' AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. Diabetes 48, 16671671.Google Scholar
Merrill, GF, Kurth, EJ, Hardie, DG & Winder, WW (1997) AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. American Journal of Physiology 273, E1107E1112.Google Scholar
Mu, J, Brozinick, JT Jr, Valladares, O, Bucan, M & Birnbaum, MJ (2001) A role for AMP-activated protein kinase in contraction-and hypoxia-regulated glucose transport in skeletal muscle. Molecular Cell 7, 10851094.Google Scholar
Musi, N, Fujii, N, Hirshman, MF, Ekberg, I, Froberg, S, Ljungqvist, O, Thorell, A & Goodyear, LJ (2001 a) AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type 2 diabetes during exercise. Diabetes 50, 921927.CrossRefGoogle ScholarPubMed
Musi, N & Goodyear, LJ (2002) Targeting the AMP-activated protein kinase for the treatment of type 2 diabetes. Current Drug Targets Immune, Endocrine and Metabolic Disorders 2, 119127.CrossRefGoogle ScholarPubMed
Musi, N, Hayashi, T, Fujii, N, Hirshman, MF, Witters, LA & Goodyear, LJ (2001 b) AMP-activated protein kinase activity and glucose uptake in rat skeletal muscle. American Journal of Physiology 280, E677E684.Google Scholar
Nielsen, JN, Wojtaszewski, JF, Haller, RG, Hardie, DG, Kemp, BE, Richter, EA & Vissing, J (2002) Role of 5'AMP-activated protein kinase in glycogen synthase activity and glucose utilization: insights from patients with McArdle's disease. Journal of Physiology (London) 541, 979989.Google Scholar
Rasmussen, BB & Winder, WW (1997) Effect of exercise intensity on skeletal muscle malonyl-CoA and acetyl-CoA carboxylase. Journal of Applied Physiology 83, 11041109.CrossRefGoogle ScholarPubMed
Richter, EA, Cleland, PJF, Rattigan, S, Clark, MG & Cleland, PJ (1987) Contraction-associated translocation of protein kinase C in rat skeletal muscle. FEBS Letters 217, 232236.CrossRefGoogle ScholarPubMed
Sakoda, H, Ogihara, T, Anai, M, Fujishiro, M, Ono, H, Onishi, Y, Katagiri, H, Abe, M, Fukushima, Y, Shojima, N, Inukai, K, Kikuchi, M, Oka, Y & Asano, T (2002) Activation of AMPK is essential for AICAR-induced glucose uptake by skeletal muscle but not adipocytes. American Journal of Physiology 282, E1239E1244.Google Scholar
Salt, I, Celler, JW, Hawley, SA, Prescott, A, Woods, A, Carling, D & Hardie, DG (1998) AMP-activated protein kinase: greater AMP dependence, and preferential nuclear localization, of complexes containing the alpha2 isoform. Biochemical Journal 334, 177187.CrossRefGoogle ScholarPubMed
Somwar, R, Perreault, M, Kapur, S, Taha, C, Sweeney, G, Ramlal, T, Kim, DY, Keen, J, Cote, CH, Klip, A & Marette, A (2000) Activation of p38 mitogen-activated protein kinase alpha and beta by insulin and contraction in rat skeletal muscle: potential role in the stimulation of glucose transport. Diabetes 49, 17941800.Google Scholar
Stapleton, D, Mitchelhill, KI, Gao, G, Widmer, J, Michell, BJ, Teh, T, House, CM, Fernandez, CS, Cox, T, Witters, LA & Kemp, BE (1996) Mammalian AMP-activated protein kinase subfamily. Journal of Biological Chemistry 271, 611614.Google Scholar
Stephens, TJ, Chen, ZP, Canny, BJ, Michell, BJ, Kemp, BE & McConell, GK (2002) Progressive increase in human skeletal muscle AMPK alpha2 activity and ACC phosphorylation during exercise. American Journal of Physiology 282, E688E694.Google Scholar
Thornton, C, Snowden, MA & Carling, D (1998) Identification of a novel AMP-activated protein kinase beta subunit isoform that is highly expressed in skeletal muscle. Journal of Biological Chemistry 273, 1244312450.Google Scholar
Vavvas, D, Apazidis, A, Saha, AK, Gamble, J, Patel, A, Kemp, BE, Witters, LA & Ruderman, NB (1997) Contraction-induced changes in acetyl-CoA carboxylase and 5'-AMP-activated kinase in skeletal muscle. Journal of Biological Chemistry 272, 1325513261.CrossRefGoogle Scholar
Vincent, MF, Marangos, P, Gruber, HE & Van den, BG (1991) AICAriboside inhibits gluconeogenesis in isolated rat hepatocytes. Advances in Experimental Medicine and Biology 309B, 359362.Google Scholar
Warden, SM, Richardson, C, O'Donnell, JJ, Stapleton, D, Kemp, BE & Witters, LA (2001) Post-translational modifications of the beta-1 subunit of AMP-activated protein kinase affect enzyme activity and cellular localization. Biochemical Journal 354, 275283.Google Scholar
Winder, WW & Hardie, DG (1999) AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. American Journal of Physiology 277, E1E10.Google ScholarPubMed
Wojtaszewski, JF, Jorgensen, SB, Hellsten, Y, Hardie, DG & Richter, EA (2002) Glycogen-dependent effects of 5-aminoimidazole-4-carboxamide (AICA)-riboside on AMP-activated protein kinase and glycogen synthase activities in rat skeletal muscle. Diabetes 51, 284292.Google Scholar
Wojtaszewski, JF, Lynge, J, Jakobsen, AB, Goodyear, LJ & Richter, EA (1999) Differential regulation of MAP kinase by contraction and insulin in skeletal muscle: Metabolic implications. American Journal of Physiology 277, E724E732.Google Scholar
Wojtaszewski, JF, Nielsen, P, Hansen, BF, Richter, EA & Kiens, B (2000) Isoform-specific and exercise intensity-dependent activation of 5'-AMP-activated protein kinase in human skeletal muscle. Journal of Physiology (London) 528, 221226.Google Scholar
Xi, X, Han, J & Zhang, JZ (2001) Stimulation of glucose transport by AMP-activated protein kinase (AMPK) via activation of p38 mitogen-activated protein kinase (MAPK). Journal of Biological Chemistry 276, 4102941034.Google Scholar
Young, JC, Kurowski, TG, Maurice, AM, Nesher, R & Ruderman, NB (1991) Polymyxin B inhibits contraction-stimulated glucose uptake in rat skeletal muscle. Journal of Applied Physiology 70, 16501654.Google Scholar
Young, ME, Radda, GK & Leighton, B (1996) Activation of glycogen phosphorylase and glycogenolysis in rat skeletal muscle by AICAR – an activator of AMP-activated protein kinase. FEBS Letters 382, 4347.Google Scholar