Immobilization in diabetic rats, results in altered glucose tolerance; A model of reduced locomotion/activity in diabetes

Silvia Busquets

Abstract


Background: Type 2 Diabetes Mellitus affects more than 350 million people worldwide. This metabolic disorder is characterized by insulin resistance, β-cell dysfunction and elevated hepatic glucose output. Patients with diabetes are hospitalized frequently (3-fold greater) and with longer admissions (30% longer) than the non-diabetic subjects. The aim of the study was to investigate the impact of bed rest on the metabolic changes in type II diabetes mellitus, with particular interest in skeletal muscle mass and function and metabolism.

Methods: 13wk old male Zucker diabetic fatty (ZDF) rats were randomly divided into two groups: control (ZDF-Con) and cage-immobilized animals (ZDF-Cage) for 28 consecutive days in a space-restricted cage.

Results: The Area Under the Curve (AUC) values for plasma glucose concentration in ZDF-Cage rats were significantly increased (approximately 4-fold as compared with ZDF-Con rats). GLUT4 gene expression in red soleus muscle of ZDF-Cage animals was reduced 2.5-fold in comparison with ZDF–Con rats. Although no apparent changes were observed either in fasting plasma glucose or insulin levels, a trend towards an increase in the HOMA-IR index and decreased levels of plasma adiponectin (-30%) were observed in ZDF-Cage animals. Moreover, ZDF-Cage rats did not lose muscle mass and force but performed a reduced total physical activity level (-22%).

Conclusions: The present study results suggests that 28 days of immobilization --in a space-restriction model-- significantly impaired glucose tolerance with concomitant reduced plasmatic adiponectin levels and GLUT-4 expression in soleus muscle of type 2 diabetic rats.

Full Text:

PDF

References


Brower P, Hicks D. Maintaining muscle function in patients on bed rest. Am J Nurs 1972;72:1250–3.

Corcoran PJ. Use it or lose it--the hazards of bed rest and inactivity. West J Med 1991;154:536–8.

Winkelman C. Bed rest in health and critical illness: a body systems approach. AACN Adv Crit Care 2009;20:254–66.

Musacchia XJ, Steffen JM, Fell RD. Disuse atrophy of skeletal muscle: animal models. Exerc Sport Sci Rev 1988;16:61–87.

Sato S, Suzuki H, Tsujimoto H, Shirato K, Tachiyashiki K, Imaizumi K. Casted-immobilization downregulates glucocorticoid receptor expression in rat slow-twitch soleus muscle. Life Sci 2011;89:962–7.

Alibegovic AC, Hojbjerre L, Sonne MP, van Hall G, Stallknecht B, Dela F et al. Impact of 9 Days of Bed Rest on Hepatic and Peripheral Insulin Action, Insulin Secretion, and Whole-Body Lipolysis in Healthy Young Male Offspring of Patients With Type 2 Diabetes. Diabetes 2009;58:2749–2756.

Stuempfle K, Drury D. The Physiological Consequences of Bed Rest. J. Exerc. Physiol. 2007.

Topp R, Ditmyer M, King K, Doherty K, Hornyak J. The effect of bed rest and potential of prehabilitation on patients in the intensive care unit. AACN Clin Issues 2002;13:263–76.

Dittmer DK, Teasell R. Complications of immobilization and bed rest. Part 1: Musculoskeletal and cardiovascular complications. Can Fam Physician 1993;39:1428–32, 1435–7.

Cantley J, Ashcroft FM. Q&A: insulin secretion and type 2 diabetes: why do β-cells fail? BMC Biol 2015;13:33.

Coughlan KA, Valentine RJ, Ruderman NB, Saha AK. AMPK activation: a therapeutic target for type 2 diabetes? Diabetes Metab Syndr Obes 2014;7:241–53.

Volpato S, Ferrucci L, Blaum C, Ostir G, Cappola A, Fried LP et al. Progression of Lower-Extremity Disability in Older Women With Diabetes: The Women’s Health and Aging Study. Diabetes Care 2003;26:70–75.

Gregg EW, Mangione CM, Cauley JA, Thompson TJ, Schwartz A V., Ensrud KE et al. Diabetes and Incidence of Functional Disability in Older Women. Diabetes Care 2002;25:61–67.

Volpato S, Blaum C, Resnick H, Ferrucci L, Fried LP, Guralnik JM. Comorbidities and impairments explaining the association between diabetes and lower extremity disability: The Women’s Health and Aging Study. Diabetes Care 2002;25:678–83.

Kalyani RR, Corriere M, Ferrucci L. Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases. lancet Diabetes Endocrinol 2014;2:819–29.

Kalyani RR, Saudek CD, Brancati FL, Selvin E. Association of diabetes, comorbidities, and A1C with functional disability in older adults: results from the National Health and Nutrition Examination Survey (NHANES), 1999-2006. Diabetes Care 2010;33:1055–60.

Krawiec BJ, Frost RA, Vary TC, Jefferson LS, Lang CH. Hindlimb casting decreases muscle mass in part by proteasome-dependent proteolysis but independent of protein synthesis. Am J Physiol Endocrinol Metab 2005;289:E969-80.

Magne H, Savary-Auzeloux I, Migné C, Peyron M-A, Combaret L, Rémond D et al. Unilateral hindlimb casting induced a delayed generalized muscle atrophy during rehabilitation that is prevented by a whey or a high protein diet but not a free leucine-enriched diet. PLoS One 2013;8:e70130.

Tesch PA, Ploutz LL, Dudley GA. Effects of 5 weeks of lower limb suspension on muscle size and strength. J Gravit Physiol 1994;1:P59-60.

Machida S, Booth FW. Regrowth of skeletal muscle atrophied from inactivity. Med Sci Sports Exerc 2004;36:52–9.

Bialek P, Morris C, Parkington J, St Andre M, Owens J, Yaworsky P et al. Distinct protein degradation profiles are induced by different disuse models of skeletal muscle atrophy. Physiol Genomics 2011;43:1075–86.

Marmonti E, Busquets S, Toledo M, Ricci M, Beltrà M, Gudiño V et al. A Rat Immobilization Model Based on Cage Volume Reduction: A Physiological Model for Bed Rest? Front Physiol 2017;8:184.

Reeves PG, Nielsen FH, Fahey GC. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 1993;123:1939–51.

Allison DB, Paultre F, Maggio C, Mezzitis N, Pi-Sunyer FX. The use of areas under curves in diabetes research. Diabetes Care 1995;18:245–50.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9.

Sárközy M, Zvara A, Gyémánt N, Fekete V, Kocsis GF, Pipis J et al. Metabolic syndrome influences cardiac gene expression pattern at the transcript level in male ZDF rats. Cardiovasc Diabetol 2013;12:16.

Ametller E, Busquets S, Fuster G, Figueras MT, De Oliveira CC, Toledo M et al. Effects of formoterol on protein metabolism in myotubes during hyperthermia. Muscle Nerve43:268–273.

Toledo M, Busquets S, Sirisi S, Serpe R, Orpí M, Coutinho J et al. Cancer cachexia: physical activity and muscle force in tumour-bearing rats. Oncol Rep 2011;25:189–93.

Abramoff MD, Magalhães PJ, Ram SJ. Image processing with ImageJ. Biophotonics Int. 2004;11:36–42.

Biolo G, Agostini F, Simunic B, Sturma M, Torelli L, Preiser JC et al. Positive energy balance is associated with accelerated muscle atrophy and increased erythrocyte glutathione turnover during 5 wk of bed rest. Am J Clin Nutr 2008;88:950–8.

DeFronzo RA, Tripathy D. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 2009;32 Suppl 2:S157-63.

Cersosimo E, Triplitt C, Mandarino LJ, DeFronzo RA. Pathogenesis of Type 2 Diabetes Mellitus. 2015.

Xu P-T, Song Z, Zhang W-C, Jiao B, Yu Z-B. Impaired translocation of GLUT4 results in insulin resistance of atrophic soleus muscle. Biomed Res Int 2015;2015:291987.

Didyk RB, Anton EE, Robinson KA, Menick DR, Buse MG. Effect of immobilization on glucose transporter expression in rat hindlimb muscles. Metabolism 1994;43:1389–1394.

Gerrits P, Olson A, Pessin J. Regulation of the GLUT4/muscle-fat glucose transporter mRNA in adipose tissue of insulin-deficient diabetic rats. J Biol Chem 1993;268:640–644.

Flores-Riveros JR, McLenithan JC, Ezaki O, Lane MD. Insulin down-regulates expression of the insulin-responsive glucose transporter (GLUT4) gene: effects on transcription and mRNA turnover. Proc Natl Acad Sci U S A 1993;90:512–516.

Zorzano A, Palacín M, Gumà A. Mechanisms regulating GLUT4 glucose transporter expression and glucose transport in skeletal muscle. Acta Physiol. Scand. 2005;183:43–58.

Unger RH. Lipotoxic diseases. Annu Rev Med 2002;53:319–336.

Rasouli N, Kern PA. Adipocytokines and the metabolic complications of obesity. J. Clin. Endocrinol. Metab. 2008;93.

Jung UJ, Choi M-S. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci 2014;15:6184–223.

Romacho T, Elsen M, Rhrborn D, Eckel J. Adipose tissue and its role in organ crosstalk. Acta Physiol. 2014;210:733–753.

Musi N, Guardado-Mendoza R. Adipose Tissue as an Endocrine Organ. In: Cellular Endocrinology in Health and Disease. 2014. pp. 229–237.

Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004;114:1752–1761.

Owecki M, Sowinski J. [Adiponectin and its role in the pathogenesis of obesity, diabetes mellitus and insulin resistance]. Pol Merkur Lek 2006;20:355–357.

Reinwald S, Peterson RG, Allen MR, Burr DB. Skeletal changes associated with the onset of type 2 diabetes in the ZDF and ZDSD rodent models. Am J Physiol Endocrinol Metab 2009;296:E765-74.

Teixeira de Lemos E, Reis F, Baptista S, Pinto R, Sepodes B, Vala H et al. Exercise training decreases proinflammatory profile in Zucker diabetic (type 2) fatty rats. Nutrition 2009;25:330–9.

Momken I, Stevens L, Bergouignan A, Desplanches D, Rudwill F, Chery I et al. Resveratrol prevents the wasting disorders of mechanical unloading by acting as a physical exercise mimetic in the rat. FASEB J 2011;25:3646–60.

Sala D, Zorzano A. Differential control of muscle mass in type 1 and type 2 diabetes mellitus. Cell Mol Life Sci 2015;72:3803–17.

Tajiri Y, Kato T, Nakayama H, Yamada K. Reduction of skeletal muscle, especially in lower limbs, in Japanese type 2 diabetic patients with insulin resistance and cardiovascular risk factors. Metab Syndr Relat Disord 2010;8:137–42.

Baltadjiev A, Baltadjiev G. Assessment of Body Composition of Male Patients with Type 2 Diabetes by Bioelectrical Impedance Analysis. Folia Med (Plovdiv) 2011;53:52–57.

Kim K-S, Park K-S, Kim M-J, Kim S-K, Cho Y-W, Park SW. Type 2 diabetes is associated with low muscle mass in older adults. Geriatr Gerontol Int 2014;14 Suppl 1:115–21.

Andersen H, Gjerstad MD, Jakobsen J. Atrophy of foot muscles: A measure of diabetic neuropathy. Diabetes Care 2004;27:2382–2385.

Leenders M, Verdijk LB, van der Hoeven L, Adam JJ, van Kranenburg J, Nilwik R et al. Patients with type 2 diabetes show a greater decline in muscle mass, muscle strength, and functional capacity with aging. J Am Med Dir Assoc 2013;14:585–92.

Park SW, Goodpaster BH, Lee JS, Kuller LH, Boudreau R, de Rekeneire N et al. Excessive loss of skeletal muscle mass in older adults with type 2 diabetes. Diabetes Care 2009;32:1993–7.

Pompeani N, Rybalka E, Latchman H, Murphy RM, Croft K, Hayes A. Skeletal muscle atrophy in sedentary Zucker obese rats is not caused by calpain-mediated muscle damage or lipid peroxidation induced by oxidative stress. J Negat Results Biomed 2014;13:153.

Marmonti E, Busquets S, Toledo M, Ricci M, Beltrà M, Gudiño V et al. A Rat Immobilization Model Based on Cage Volume Reduction: A Physiological Model for Bed Rest? Front Physiol 2017;8:184.

Järvinen TAH, Józsa L, Kannus P, Järvinen TLN, Järvinen M. Organization and distribution of intramuscular connective tissue in normal and immobilized skeletal muscles. An immunohistochemical, polarization and scanning electron microscopic study. J Muscle Res Cell Motil 2002;23:245–54.

Appell HJ. Muscular atrophy following immobilisation. A review. Sports Med 1990;10:42–58.

Cetinus E, Buyukbese MA, Uzel M, Ekerbicer H, Karaoguz A. Hand grip strength in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2005;70:278–86.

Rantanen T. Muscle strength, disability and mortality. Scand J Med Sci Sport 2003;13:3–8.

Ikai M, Fukunaga T. Calculation of muscle strength per unit cross-sectional area of human muscle by means of ultrasonic measurement. IInt Z Angew Physiol 1968;26:26–32.

Räty HP, Kujala U, Videman T, Koskinen SK, Karppi SL, Sarna S. Associations of isometric and isoinertial trunk muscle strength measurements and lumbar paraspinal muscle cross-sectional areas. J Spinal Disord 1999;12:266–70.

Lynch GS. Therapies for improving muscle function in neuromuscular disorders. Exerc Sport Sci Rev 2001;29:141–8.

Zinna EM, Yarasheski KE. Exercise treatment to counteract protein wasting of chronic diseases. Curr Opin Clin Nutr Metab Care 2003;6:87–93.

Busquets S, Toledo M, Sirisi S, Orpí M, Serpe R, Coutinho J et al. Formoterol and cancer muscle wasting in rats: Effects on muscle force and total physical activity. Exp Ther Med 2011;2:731–735.

von Haehling S, Morley JE, Coats AJS, Anker SD. Ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle: update 2015. J Cachexia Sarcopenia Muscle 2015;6:315–316.


Refbacks

  • There are currently no refbacks.