Investigation of the relationship between plasma ghrelin levels and muscle atrophy in experimental diabetic rats
Author:
Keşim D. Aygün1, Kelle M.1, Aşır F.2, Kaya H. Kayhan1, Diken H.1, Gökdemir G.Ş.3, Direk F. Koç4
Affiliation:
1. Department of Physiology, Medical Faculty, Dicle University, Sur, 21280, Diyarbakır, Turkey 2. Department of Histology and Embryology, Medical Faculty, Dicle University, Sur, 21280, Diyarbakır, Turkey 3. Department of Physiology, Medical Faculty, Mardin Artuklu University, Artuklu, 47200, Mardin, Turkey 4. Department of Anatomy, Medical Faculty, Mardin Artuklu University, Artuklu, 47200, Mardin, Turkey
Abstract
In this study, the relationship between plasma ghrelin levels and muscle atrophy was examined in an experimental diabetic rat model. 56 male Wistar albino rats, aged 8-10 weeks, were used in the study. The rats were divided into 8 groupsD1: one-week diabetes, C1: one-week control, D2: three-week diabetes, C2: three-week control, D3: six-week diabetes, C3: six-week control, D4: eight-week diabetes, C4: eight-week control. To induce diabetes, rats were injected with a single intraperitoneal dose of 45 mg/kg streptozotocin. At the end of the experiments, body weights and fasting blood sugar levels were measured. mTOR and myostatin levels of gastrocnemius muscle and plasma ghrelin levels were measured by ELISA method. Gastrocnemius muscle weight, cross-sectional area and histopathological images were examined. It was observed that the gastrocnemius weights of the D2, D3, D4 groups decreased significantly compared to their controls (p≤0.01). Muscle cross-sectional area decreased significantly in groups D3 and D4 compared to controls (p≤0.01). Muscle mTOR levels were found to be significantly lower in all diabetic groups compared to controls (p≤0.01). Although muscle myostatin levels were higher in the diabetic groups, this increase was only significant in the D4 group. Plasma ghrelin levels were significantly lower in all diabetic groups compared to controls (p≤0.01). A positive correlation was determined between plasma ghrelin levels and the final weights, muscle cross-sectional area, gastrocnemius weights and mTOR levels of the rats. Time-dependent muscle atrophy developed in diabetic rats and there was a relationship between muscle atrophy and plasma ghrelin level. We suggest that ghrelin plays a role in diabetes-induced muscle atrophy as well as cachexia and sarcopenia.
Publisher
Polish Academy of Sciences Chancellery
Reference1 articles.
1. Ali S, Garcia JM (2014) Sarcopenia, cachexia and aging: diagnosis, mechanisms and therapeutic options - a mini-review. Gerontology 60: 294-305. Argilés JM, Campos N, Lopez-Pedrosa JM, Rueda R, Rodriguez-Mañas L (2016) Skeletal muscle regulates metabolism via interorgan crosstalk: roles in health and disease. J Am Med Dir Assoc 17: 789-796. Ato S, Kido K, Sato K, Fujita S (2019) Type 2 diabetes causes skeletal muscle atrophy but does not impair resistance training‐mediated myonuclear accretion and muscle mass gain in rats. Exp Physiol 104: 1518-1531. Gortan Cappellari G, Barazzoni R (2019) Ghrelin forms in the modulation of energy balance and metabolism. Eat Weight Disord 24: 997-1013. Cohen S, Nathan JA, Goldberg AL (2015) Muscle wasting in disease: molecular mechanisms and promising therapies. Nat Rev Drug Discov 14: 58-74. Coleman SK, Rebalka IA, D’souza DM, Deodhare N, Desjardins EM, Hawke TJ. (2016) Myostatin inhibition therapy for insulin-deficient type 1 diabetes. Sci Rep 6: 32495. Doustar Y, Salehi I, Mohamadi M, Mohajeri D, Hashemi M (2007) Investigate the effect of regular exercise on diabetic nephropathy in rat. Medi-cal Sci J 17: 187- 193. D’Souza DM, Al-Sajee D, Hawke TJ (2013) Diabetic myopathy: impact of diabetes mellitus on skeletal muscle progenitor cells. Front Physiol 4: 379. Elkina Y, von Haeling S, Anker SD, Springer J (2011) The role of myostatin in muscle wasting: an overview. J Cachexia Sarcopenia Muscle 2: 143-151. Elsawy M, Emara E (2016) The impact of ghrelin on oxidative stress and inflammatory markers on the liver of diabetic rats. Tanta Med J 44: 163-169. Evans PL, McMillin SL, Weyrauch LA, Witczak CA (2019) Regulation of Skeletal Muscle Glucose Transport and Glucose Metabolism by Exer-cise Training. Nutrients 11: 2432. Garcia JM, Cata JP, Dougherty PM, Smith RG (2008) Ghrelin prevents cisplatin-induced mechanical hyperalgesia and cachexia. Endocrinology 149: 455-60. International Diabetes Federation (2019) IDF Diabetes Atlas. 9th ed. Brussels, Belgium: International Diabetes Federation. Kavishankar GB, Lakshmidevi N (2014) Anti-diabetic effect of a novel N-Trisaccharide isolated from Cucumis prophetarum on streptozoto-cin–nicotinamide induced type 2 diabetic rats. Phytomedicine 21: 624-630. Lambertucci AC, Lambertucci RH, Hirabara SM, Curi R, Moriscot AS, Alba-Loureiro TC, Guimarães-Ferreira L, Levada-Pires AC, Vasconcelos DA, Sellitti DF, Pithon-Curi TC (2012) Glutamine supplementation stimulates protein-synthetic and inhibits protein-degradative signaling pathways in skeletal muscle of diabetic rats. PLoS One 7: e50390. Nguyen MH, Cheng M, Koh TJ (2011) Impaired muscle regeneration in ob/ob and db/db mice. ScientificWorldJournal 11: 1525-1535. Nowak N, Hohendorff J, Solecka I, Szopa M, Skupien J, Kiec-Wilk B, Mlynarski W, Malecki MT (2015) Circulating ghrelin level is higher in HNF1A-MODY and GCK-MODY than in polygenic forms of diabetes mellitus. Endocrine 50: 643-649. Perry BD, Caldow MK, Brennan-Speranza TC, Sbaraglia M, Jerums G, Garnham A, Wong C, Levinger P, Asrar Ul Haq M, Hare DL, Price SR, Levinger I (2016) Muscle atrophy in patients with Type 2 Diabetes Mellitus: roles of inflammatory pathways, physical activity and exercise. Exerc Immunol Rev 22: 94-109. Porporato PE, Filigheddu N, Reano S, Ferrara M, Angelino E, Gnocchi VF, Prodam F, Ronchi G, Fagoonee S, Fornaro M, Chianale F, Baldanzi G, Surico N, Sinigaglia F, Perroteau I, Smith RG, Sun Y, Geuna S, Graziani A (2013) Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice. J Clin Invest 123(2): 611-622. Pöykkö SM, Kellokoski E, Hörkkö S, Kauma H, Kesäniemi YA, Ukkola O (2003) Low plasma ghrelin is associated with insulin resistance, hy-pertension, and the prevalence of type 2 diabetes. Diabetes 52: 2546-53. Prodam F, Cadario F, Bellona S, Trovato L, Moia S, Pozzi E, Savastio S, Bona G (2014) Obestatin levels are associated with C-peptide and anti-insulin antibodies at the onset, whereas unacylated and acylated ghrelin levels are not predictive of long-term metabolic control in children with type 1 diabetes. J Clin Endocrinol Metab 99: E599-607. Pulkkinen L, Ukkola O, Kolehmainen M, Uusitupa M (2010) Ghrelin in diabetes and metabolic syndrome. Intl J Pept 2010: 248948. Ramesh B, Pugalendi KV (2009) Antihyperglycemic effect of umbelliferone in streptozotocin-diabetic rats. J Med Food 9: 562-566. Shankar K, Gupta D, Mani BK, Findley BG, Osborne-Lawrence S, Metzger NP, Liu C, Berglund ED, Zigman JM (2020) Ghrelin protects against insulin-induced hypoglycemia in a mouse model of Type 1 diabetes mellitus. Front in Endocrinol (Lausanne) 11: 606. Su Z, Robinson A, Hu L, Klein JD, Hassounah F, Li M, Wang H, Cai H, Wang XH. (2015) Acupuncture plus Low-Frequency Electrical Stimula-tion (Acu-LFES) Attenuates Diabetic Myopathy by Enhancing Muscle Regeneration. PLoS One 10: e0134511. Talbot J, Maves L (2016) Skeletal muscle fiber type: using insights from muscle developmental biology to dissect targets for susceptibility and resistance to muscle disease. Wiley Interdiscip Rev Dev Biol 5: 518-534. Watson K, Baar K (2014) mTOR and the health benefits of exercise. Semin Cell Dev Biol 36: 130-139. Wood N, Straw S, Scalabrin M, Roberts L (2021) Skeletal muscle atrophy in heart failure with diabetes: from molecular mechanisms to clinical evidence. ESC Heart Fail 8: 3-15. Wu CS, Wei Q, Wang H, Kim DM, Balderas M, Wu G, Lawler J, Safe S, Guo S, Devaraj S, Chen Z, Sun Y (2020) Protective Effects of Ghrelin on Fasting-Induced Muscle Atrophy in Aging Mice. J Gerontol A Biology Sci Med Sci 75: 621-630. Zinna EM, Yarasheski KE (2003) Exercise treatment to counteract protein wasting of chronic diseases. Curr Opin Clin Nutr Metab Care 6: 87-93.
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