Abstract
Background: Previously some studies have implicated erythropoietin (EPO) signalling in the regulation of glucose metabolism. Whether EPO can be used treat diabetes and the exact underlying mechanism remain to be elucidated. The present study aimed to investigate whether EPO affects glucose levels, and the underlying mechanisms, in experimental diabetic rats. The effects of EPO (40, 100 & 300 IU/kg three times a week for 4 weeks) on glucose metabolism in streptozotocin, nicotinamide induced diabetic albino rats was studied here.
Methods: 30 albino rats were taken and divided into five groups of six rats in each group. The groups were normal control, diabetic control, diabetic rats treated with EPO in doses of 40,100 and 300 IU/Kg in the last three groups. Diabetes was induced in four groups by intraperitoneal injection of streptozotocin in the dose of 60 mg/kg. To have an ideal type 2 diabetes model nicotinamide was administered 120 mg/ kg intraperitoneally fifteen minutes before streptozotocin administration. After successful induction of diabetes EPO (40,100 and 300 IU/kg, three times a week) was given to the respective groups for a period of 4 weeks. Fasting blood glucose was estimated on day 0, 7, 14, 21 and 28 of treatment.
Results: In this study EPO showed significant anti-hyperglycaemic effect in all the three groups receiving EPO (p<0.05 in all 3 groups).
Conclusions: From this study we can conclude that EPO has a marked anti-hyperglycaemic effect and the effect is dose dependent. Further studies are required at different doses to establish the optimum dose for its use as an anti-diabetic drug and to alleviate or avoid the adverse effects before it can be used for the treatment of diabetes or its complications.
Keywords: EPO (Erythropoietin), Diabetes mellitus (DM), Fasting blood glucose, Streptozotocin.
References
- Alvin C Powers. Diabetes Mellitus: Diagnosis, Classification and Pathophysi-ology. Harrison’s principles of internal medicine. 19thedition. 2015;417:2399-2407.
- Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res ClinPract 2010;87:4-14.
- Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047-53.
- Obara, N., Suzuki, N., Kim, K., Nagasawa, T., Imagawa, S., Yamamoto, M., 2008. Repression via the GATA box is essential for tissue-specific erythropoietin gene expression. Blood 111, 5223– 5232.
- E. S. Fenjves, M. S. Ochoa, O. Cabrera, A. J. Mendez, N. S. Kenyon, L. Inverardi, and C. Ricordi, “Human, nonhuman primate, and rat pancreatic islets express erythropoietin receptors.,” Transplantation vol. 75, no. 8, pp. 1356–60, Apr. 2003.
- Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire-Buys D, et al. Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide.Diabetes. 1998 Feb 1;47(2):224-9.
- Choi D, Woo M, et al Erythropoietin protects against diabetes through direct effects on pancreatic cells. J. Exp. Med. Vol. 207 No. 13 2831-2842
- Niu HS. Erythropoietin ameliorates hyperglycemia in type 1-like diabetic rats. Drug Design, Development and Therapy 2016:10 1877–1884.
- Chen LN. Erythropoietin improves glucose metabolism and pancreatic β-cell damage in experimental diabetic rats. Molecular medicine reports 2015. https://doi.org/10.3892/mmr.2015.4006
- Katz O, Neumann D et al. Erythropoietin treatment leads to reduced blood glucose levels and body mass: insights from murine models. Journal of Endocrinology. April 1, 2010 205 87-95
- Desouki N.I.E et al. Improvement in beta-islets of Langerhans in alloxan-induced diabetic rats by erythropoietin and spirulina. The Journal of Basic & Applied Zoology (2015) 71, 20–31
- Jelkmann K. Physiology and Pharma-cology of Erythropoietin. Transfusion Medicine Hemotherapy 2013;40:302–309
- Watanabe M. A Non Haematopoietic Erythropoietin Analogue, ARA 290, Inhibits Macrophage Activation and Prevents the Transplanted Islet Graft Damage. Am J Transplant. 2015; 15 (suppl 3).
- Nakamura M, Nagafuchi S, Yamaguchi K, TakakiR. :The role of thymic immunity and insulitis in the development of streptozocin-induced diabetes in mice. Diabetes. 1984 Sep;33(9):894–900. Bell RC,
- Collino M et al. A non-erythropoietic peptide derivative of erythropoietin decreases susceptibility to diet-induced insulin resistance in mice. British Journal of Pharmacology (2014) 171 5802–5815.
Corresponding Author
Vineet Kumar
Department of Pharmacology, RIMS, Ranchi, India
Mob no 9038582331, Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
DOI: https://dx.doi.org/10.18535/jmscr/v6i2.143
