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DOI: 10.1055/s-0031-1271747
© Georg Thieme Verlag KG Stuttgart · New York
Exercise-stimulated GLUT4 Expression is Similar in Normotensive and Hypertensive Rats
Publication History
received 29.07.2010
accepted after second revision 18.01.2011
Publication Date:
17 February 2011 (online)
Abstract
The effects of exercise training on systolic blood pressure (BP), insulin sensitivity, and plasma membrane GLUT4 protein content in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were compared. 16 SHR and 16 WKY male rats, aged 6 months, were randomized into sedentary and trained (treadmill running, 5 days/week, 60 min/day for 10 weeks) groups (n=8/group). At baseline, SHR had lower insulin sensitivity than WKY rats, however, there were no differences between WKY and SHR GLUT4 expression. The 10-week training reduced BP by ∼19% in SHR, improved insulin sensitivity by ∼24% in SHR, but not in WKY, and increased GLUT4 expression in both animal models. Compared to the sedentary group, there was an increase of GLUT4 in WKY rats by ∼25% in the heart, by ∼23% in the gastrocnemius, and by ∼15% in the fat tissue. Trained SHR presented an increase in GLUT4 of ∼21%, ∼20%, and ∼14%, in the same tissues, respectively. There were no differences between SHR and WKY rats in post-training GLUT4 expression. We conclude that training determined BP and insulin resistance reduction in SHR, and increased GLUT4 expression in both normotensive and hypertensive rats. However, considering the similar rise in GLUT4-induced training in SHR and WKY, it is possible that GLUT4 levels in plasma membrane fraction do not have a pivotal role in the exercise-induced improvement of insulin sensitivity in SHR.
Key words
glucose transporter type 4 - exercise training - insulin resistance - hypertension
References
- 1 James DJ, Cairns F, Salt IP, Murphy GJ, Dominiczak AF, Connell JM, Gould GW. Skeletal muscle of stroke-prone spontaneously hypertensive rats exhibits reduced insulin-stimulated glucose transport and elevated levels of caveolin and flotillin. Diabetes. 2001; 50 2148-2156
- 2 Cingolani G, Caldiz C. Insulin resistance and GLUT-4 glucose transporter in adipocytes from hypertensive rats. Metabolism. 2004; 53 382-387
- 3 de Carvalho Papa P, Vargas AM, da Silva JL, Nunes MT, Machado UF. GLUT4 protein is differently modulated during development of obesity in monosodium glutamate-treated mice. Life Sci. 2002; 71 1917-1928
- 4 De Angelis Lobo d’Avila K, Gadonski G, Fang J, Dall’Ago P, Albuquerque VL, Peixoto LR, Fernandes TG, Irigoyen MC. Exercise reverses peripheral insulin resistance in trained L-NAME-hypertensive rats. Hypertension. 1999; 34 768-772
- 5 Lira V, Soltow Q, Long J, Betters J, Sellman J. Nitric oxide increases GLUT4 expression and regulates AMPK signaling in skeletal muscle. Am J Physiol Endocrinol Metab. 2007; 293 E1062-E1068
- 6 Tipton C, Sebastian L, Overton J, Woodman C, Williams S. Chronic exercise and its hemodynamic influences on resting blood pressure of hypertensive rats. J Appl Physiol. 1991; 71 2206-2210
- 7 Whelton S, Chin A, Xin X, He J. Effects of aerobic exercise on blood pressure: A meta-analysis of randomized controlled trials. Ann/intern Med. 2002; 136 493-503
- 8 Gava N, Veras-Silva A, Negrão C, Krieger EM. Low-intensivity exercise training attenuates cardiac B-adrenergic tone during exercise in spontaneously hypertensive rats. Hypertension. 1995; 26 1129-1133
- 9 Graham D, Rush J. Exercise training improves aortic endothelium-dependent vasorelaxation and determinants of nitric oxide bioavailability in spontaneously hypertensive rats. J Appl Physiol. 2004; 96 2088-2096
- 10 Song Y, Sawamura M, Ikeda K, Igawa S, Nara Y, Yamori Y. Training in swimming reduces blood pressure and increases muscle glucose transport activity as well as GLUT4 contents in stroke-prone spontaneously hypertensive rats. Appl Human Sci. 1998; 17 275-280
- 11 Lehnen AM, Leguisamo NM, Pinto GH, Markoski MM, De Angelis K, Machado UF, Schaan B. The beneficial effects of exercise in rodents are preserved after detraining: a phenomenon unrelated to GLUT4 expression. Cardiovascular Diabetology. 2010; 9 67
- 12 Jessen N, Selmer Buhl E, Pold R, Schmitz O, Lund S. A novel insulin sensitizer (S15511) enhances insulin-stimulated glucose uptake in rat skeletal muscles. Horm Metab Res. 2008; 40 269-275
- 13 Fogari R, Zoppi A, Ferrari I, Mugellini A, Preti P, Lazzari P, Derosa G. Comparative effects of telmisartan and eprosartan on insulin sensitivity in the treatment of overweight hypertensive patients. Horm Metab Res. 2009; 41 893-898
- 14 Garvey W, Malanu L, Zhu J, Brechtel-Hook G, Wallace P, Baron A. Evidence of the defects in trafficking and translocation of GLUT4 glucose transporter in skeletal muscle as a cause of human insulin resistance. J Clin Invest. 1998; 101 2377-2386
- 15 Carvalho E, Jansson PA, Nagaev I, Wenthzel AM, Smith U. Insulin resistance with low cellular IRS-1 expression is also associated with low GLUT4 expression and impaired insulin-stimulated glucose transport. Faseb J. 2001; 15 1101-1113
- 16 Pfeffer J, Pfeffer M, MC F, ED F. Cardiac function and morphology with aging in the spontaneously hypertensive rat. Am J Physiol. 1979; 237 H461-H468
- 17 Katayama S, Inaba M, Maruno Y, Morita T, Awata T, Oka Y. Glucose intolerance in spontaneously hypertensive and wistar-kyoto rats: enhanced gene expression and synthesis of skeletal muscle glucose transporter 4. Hypertens Res. 1997; 20 279-286
- 18 NIH .Guide for the Care and Use of Laboratory Animals. Washington, DC: National Academy Press; 1996: 21-70
- 19 Rodrigues B, Figueroa D, Mostarda C, Heeren M, Irigoyen M, De Angelis K. Maximal exercise test is a useful method for physical capacity and oxygen consumption determination in streptozotocin-diabetic rats. Cardiovasc Diabetol. 2007; 6 38
- 20 Host H, Hansen P, Nolte L, Chen M, Holloszy J. Rapid reversal of adaptive increases in muscle GLUT4 and glucose transport capacity after cessation of training. J Appl Physiol. 1998; 84 798-802
- 21 Mori RC, Hirabara SM, Hirata AE, Okamoto MM, Machado UF. Glimepiride as insulin sensitizer: increased liver and muscle responses to insulin. Diabetes Obes Metab. 2008; 10 596-600
- 22 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72 248-254
- 23 Klein D, Kern RM, Sokol RZ. A method for quantification and correction of proteins after transfer to immobilization membranes. Biochem Mol Biol Int. 1995; 36 59-66
- 24 Collison M, James D, Grahan D, Homan G, Connell J, Dominiczak A, Gould G, Salt I. Reduced insulin-stimulated GLUT4 bioavailability in stroke-prone spontaneously hypertensive rats. Diabetologia. 2005; 48 539-546
- 25 Joost HG, Bell GI, Best JD, Birnbaum MJ, Charron MJ, Chen YT, Doege H, James DE, Lodish HF, Moley KH, Moley JF, Mueckler M, Rogers S, Schurmann A, Seino S, Thorens B. Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators. Am J Physiol Endocrinol Metab. 2002; 282 E974-E976
- 26 Thai M, Guruswamy S, Cao K, Pessin J, Olson A. Myocyte enhancer factor 2 (MEF2)-binding site is required for GLUT4 gene expression in transgenic mice. Regulation od MEF2 DNA binding activity in insulin-deficient diabetes. J Biol Chem. 1998; 273 285-292
- 27 McGee S, Spasling D, Olson A, Hargreaves M. Exercise increases MEF2- and GEF DNA binding activity in human skeletal muscle. FASEB J. 2006; 20 348-359
- 28 Sparling D, Griesel B, Weems J, Olson A. GLUT4 Enhancer Factor (GEF) interacts with MEF2A and HDAC5 to regulate the GLUT4 Promoter in adipocytes. Journal of Biological Chemistry. 2008; 282 7429-7447
- 29 Kurth E, Hirshman M, Goodyear L, Winder W. 5’AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. Diabetes. 1999; 48 1667-1671
- 30 Treebak JT, Glund S, Deshmukh A, Klein DK, Long YC, Jensen TE, Jorgensen SB, Viollet B, Andersson L, Neumann D, Wallimann T, Richter EA, Chibalin AV, Zierath JR, Wojtaszewski JF. AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits. Diabetes. 2006; 55 2051-2058
- 31 Kramer HF, Witczak CA, Fujii N, Jessen N, Taylor EB, Arnolds DE, Sakamoto K, Hirshman MF, Goodyear LJ. Distinct signals regulate AS160 phosphorylation in response to insulin, AICAR, and contraction in mouse skeletal muscle. Diabetes. 2006; 55 2067-2076
- 32 Smith J, Collins M, Grobler L, Magee C, Ojuka E. Exercise and CaMK activation both increase the binding of MEF2A to the GLUT4 promoter in skeletal muscule in vivo. Am J Physiol Endocrinol Metab. 2007; 292 E413-E420
- 33 Dolinsky VW, Chan AY, Robillard Frayne I, Light PE, Des Rosiers C, Dyck JR. Resveratrol prevents the prohypertrophic effects of oxidative stress on LKB1. Circulation. 2009; 119 1643-1652
- 34 Wright D, Hucker K, Holloszy J, Han D. Ca2+ and AMPK both mediate stimulation of glucose transport by muscle contractions. Diabetes. 2004; 53 330-335
- 35 Sakamoto K, Goransson O, Hardie DG, Alessi DR. Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR. Am J Physiol Endocrinol Metab. 2004; 287 E310-E327
- 36 Wu H, Rothermel B, Kanatous S, Rosenberg P, Naya FJ, Shelton JM, Hutcheson KA, DiMaio JM, Olson EN, Bassel-Duby R, Williams RS. Activation of MEF2 by muscle activity is mediated through a calcineurin-dependent pathway. Embo J. 2001; 20 6414-6423
- 37 Sriwijitkamol A, Ivy JL, Christ-Roberts C, DeFronzo RA, Mandarino LJ, Musi N. LKB1-AMPK signaling in muscle from obese insulin-resistant Zucker rats and effects of training. Am J Physiol Endocrinol Metab. 2006; 290 E925-E932
- 38 Higaki Y, Hirshman MF, Fujii N, Goodyear LJ. Nitric oxide increases glucose uptake through a mechanism that is distinct from the insulin and contraction pathways in rat skeletal muscle. Diabetes. 2001; 50 241-247
- 39 Chou TC, Yen MH, Li CY, Ding YA. Alterations of nitric oxide synthase expression with aging and hypertension in rats. Hypertension. 1998; 31 643-648
- 40 Chien CS, Cheng SC, Wu HT, Tsao CW, Cheng JT. Insulin resistance induced by glucosamine in fructose-fed rats. Horm Metab Res. 2009; 41 542-547
Correspondence
Dra. B. Schaan
Instituto de Cardiologia do Rio
Grande do Sul
Av. Princesa Isabel
395 Santana
90620-001 Porto Alegre
RS Brazil
Phone: +55/51/3230 3600 (3636/3757)
Fax: +55/51/3230 3600 (3757)
Email: beatrizschaan@gmail.com
Email: amlehnen@terra.com.br