EFFECT OF LEVOCARNITINE ON ENDURANCE CAPACITY IN TYPE-2 DIABETIC RATS
AbstractBackground: Carnitine is an essential cofactor for the enzymes transporting long chain fatty acids across mitochondrial membranes for beta oxidation and also modulates the intra-mitochondrial acylCoA/CoA ratio. This study was conducted to determine the effect of levo-carnitine on endurance capacity, skeletal muscle fatigue characteristics and glycogen stores in diabetic rats. Methods: This laboratory based experimental study was conducted in department of Physiology, Army Medical College, Rawalpindi, in collaboration with National Institute of Health (NIH), Islamabad, from June 2009 to July 2010. The study was carried on 60 healthy male Sprague-Dawley rats. Serum creatine phosphorkinase (CPK) levels were measured to exclude skeletal muscle disorder. Rats were fed high fat diet (2 weeks) followed by intra-peritoneal injection of streptozocin (35 mg/kg). On 21st day, after confirmation of type 2 diabetes by measuring plasma glucose and TG/HDL ratio, rats were divided into 2 equal groups; group I (Diabetic) and group II (Carnitine). Group II was administered l-carnitine (200mg/kg) for 6 days. Both groups were further subdivided into 2 equal groups- a (swim group) and b (non-swim group). At end of 4th week, the rats of swim group were subjected to swimming test. The extensor digitorum muscle (EDL) of rats of non-swim group was dissected for evaluation of skeletal muscle fatigue characteristics. The glycogen content of EDL muscle and serum free carnitine (FC) levels of all groups were measured. Results: Carnitine treated rats exhibited improvement in swim time as well as skeletal muscle glycogen stores (p<0.001). Significant improvement was also observed in skeletal muscle fatigue characteristics (p<0.05). Serum free carnitine levels were also significantly raised in carnitine groups; the swim groups showed a lower FC levels as compared to their respective non-swim groups (p<0.001). Conclusion: Levo-carnitine increases the glycogen stores and improves the skeletal muscle fatigue characteristics, leading to improvement in endurance capacity in type 2 diabetic rats.Keywords: type 2 diabetes, levo-carnitine, endurance, skeletal muscle, muscle glycogen store
Kraemer WJ, Volek JS, Spiereing BA, Vingren JL. L-carnitine supplementation: A new paradigm for its role in exercise. Monatshefte fur Chemie 2005;136:1383–90.
Mingrone G, Greco AV, Capristo E, Benedetti G, Giancaterini A, De Gaetano A, et al. L-carnitine improves glucose disposal in type 2 diabetic patients. J Am Coll Nutr 1999;18:77–82.
He J, Kelley DE. Muscle glycogen content in type 2 diabetes mellitus. Am J Physiol Endocrinol Metab 2004;287:1002–7.
Barnes BR, Glund S, Long YC, Hjälm G, Andersson L, Zierath JR. 5'-AMP-activated protein kinase regulates skeletal muscle glycogen content and ergogenics. FASEB J 2005;19:773–9.
Bremer J. Carnitine-metabolism and functions. Physiol Rev 1983;63:1420–80.
Friolet R, Hoppeler H, Krähenbuhl S. Relationship between the coenzyme A and the carnitine pools in human skeletal muscle at rest and after exhaustive exercise under normoxic and acutely hypoxic conditions. J Clin Invest 1994;94:1490–5.
Ferrari R, Merli E, Cicchitelli G, Mele D, Fucili A, Ceconi C. Therapeutic effects of L-carnitine propionyl-L-carnitine on cardiovascular diseases: a review. Ann N Y Acad Sci 2004;1033:79–91.
Brass EP. Pharmacokinetic considerations for the therapeutic use of carnitine in haemodialysis patients. Clin Ther 1995;17:176–85.
Brass EP, Scarrow AM, Ruff LJ, Masterson KA, Van Lunteren E. Carnitine delays rat skeletal muscle fatigue in vitro. J Appl Physiol 1993;75:1595–1600.
Cavazza C. Composition for the prevention of muscle fatigue and skeletal muscle adaptation of strenuous exercise. [Serial online] US Patent 2003 Aug 5. Available from URL: http://www.patentstorm. us/patents/6602512-description.
Coria-Avila GA, Gavrila AM, Ménard S, Ismail N, Pfaus JG. Cecum location in rats and the implications for intraperitoneal injections. Lab Anim (NY) 2007;36(7):25–30.
Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: A model for type 2 diabetes and pharmacological screening. Pharmacol Res 2005;52:313–20.
Yassin MM, Mwafy SN. Protective potential of glimepiride and nerium oleander extract on lipid profile, body growth rate, and renal function in streptozotocin-induced diabetic rats. Turk J Biol 2007;31:95–103.
McLaugin T, Abbasi F, Cheal K, Chu J, Lamendola C, Reaven G. Use of metabolic markers to identify overweight individuals who are insulin resistant. Ann Intern Med 2003;139:802–9.
Frank P, Schoenhard GL, Burton E. A method for rapid and frequent blood collection from the rat tail vein. J Pharmacol Methods 1991;26:233–8.
Nutter PE. Depletion of tissue glycogen during fasting and fatigue and partial recovery without food. J Nutr 1941;21:477–88.
Fushiki T, Matsumoto K, Inoue K, Kawada T, Sugimoto E. Swimming endurance capacity of mice is increased by chronic consumption of medium-chain triglycerides. J Nutr 1995;125:531–9.
Warmington SA, Tolan R, McBennett S. Functional and histological characteristics of skeletal muscle and the effects of leptin in the genetically obese (ob/ob) mouse. Int J Obes Relat Metab Disord 2000;24:1040–50.
Barclay CJ. Efficiency of fast- and slow-twitch muscles of the mouse performing cyclic contractions. J Exp Biol 1994;193:65–78.
Carrol NV, Lonley RW, Roe JH. The determination of glycogen in liver and muscle by use of anthrone reagent. J Biol Chem 1956;220:583–93.
Vollestad NK, Blom PCS. Effects of varying intensity to glycogen depletion in human muscle fibres. Acta Physiol Scand 1985:125:395–405.
Green HJ. How important is endogenous muscle glycogen to fatigue in prolonged exercise? Can J Physiol Pharmacol 1991;69:290–7.
Mu J, Barton ER, Birnbaum MJ. Selective suppression of AMP-activated protein kinase in skeletal muscle: update on ‘lazy mice’. Biochem Soc Trans 2003;31:236–41.
James DE, Jenkins AB, Kraegen EW. Heterogeneity of insulin action in individual muscles in vivo: euglycemic clamp studies in rats. Am J Physiol 1985;248:E567–E574.
Bruton JD, Katz A, Lännergren J, Abbate F, Westerblad H. Regulation of myoplasmic Ca(2+) in genetically obese (ob/ob) mouse single muscle skeletal fibres. Pflugers Arch 2002;444:692–9.
Uziel G, Garavaglia B, Di Donato S. Carnitine stimulation of pyruvate dehydrogenase complex (PDHC) in isolated human skeletal muscle mitochondria. Muscle Nerve 1988;11:720–4.
Barnett C, Costill DL, Vukovich MD, Cole KJ, Goodpaster BH, Trappe SW, et al. Effect of L-carnitine supplementation on muscle and blood carnitine content and lactate accumulation during high-intensity sprint cycling. Int J Sports Nutr 1994;4:280–8.
Tamamogullari N, Silig Y, Icagasioglu S, Atalay A. Carnitine deficiency in diabetes mellitus complications. J Diabet Complications 1999;13(5–6):251–3.
Sahlin K. Muscle carnitine metabolism during incremental dynamic exercise in humans. Acta Physiol Scand 1990;138:259–62.
Van Loon LJ, Greenhaff PL, Constantin-Teodosiu D, Saris WH, Wagenmakers AJ. The effects of increasing exercise intensity on muscle fuel utilization in humans. J Physiol 2001;536(Pt 1):295–304
Journal of Ayub Medical College, Abbottabad is an OPEN ACCESS JOURNAL which means that all content is FREELY available without charge to all users whether registered with the journal or not. The work published by J Ayub Med Coll Abbottabad is licensed and distributed under the creative commons License CC BY ND Attribution-NoDerivs. Material printed in this journal is OPEN to access, and are FREE for use in academic and research work with proper citation. J Ayub Med Coll Abbottabad accepts only original material for publication with the understanding that except for abstracts, no part of the data has been published or will be submitted for publication elsewhere before appearing in J Ayub Med Coll Abbottabad. The Editorial Board of J Ayub Med Coll Abbottabad makes every effort to ensure the accuracy and authenticity of material printed in J Ayub Med Coll Abbottabad. However, conclusions and statements expressed are views of the authors and do not reflect the opinion/policy of J Ayub Med Coll Abbottabad or the Editorial Board.
USERS are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author. This is in accordance with the BOAI definition of open access.
AUTHORS retain the rights of free downloading/unlimited e-print of full text and sharing/disseminating the article without any restriction, by any means including twitter, scholarly collaboration networks such as ResearchGate, Academia.eu, and social media sites such as Twitter, LinkedIn, Google Scholar and any other professional or academic networking site.