Ranolazine improves glucose and lipid homoestasis in streptozotocin induced diabetes mellitus in albino wistar rats
Keywords:Ranolazine, Plasma glucose, Lipid profile, STZ induced diabetes
Background: Type 2 diabetes mellitus is one of the most common metabolic disorders at present with increasing incidence worldwide. The disease progresses with eventual multi-system involvement such as adverse cardiovascular outcomes. This necessitates pharmacotherapy which is able to retard disease progression, have a favourable cardiovascular profile in addition to stabilisation of glucose homeostasis. Ranolazine is an anti-anginal drug, which has been shown to reduce HbA1c in patients with CAD and diabetes in various clinical trials.
Methods: Albino wistar rats of either sex weighing 150-200 grams, bred in central animal facility of JSS Medical College were used for the study. The animals were randomly divided into three groups of six animals each. Diabetes was induced in all 3 groups of animals by injecting streptozotocin in a dose of 45 mg/kg. After 72 hours of STZ administration, rats with blood glucose levels greater than 250 mg/dl were selected for the study. Capillary blood glucose levels were measured on 0, 7th, 14th, 21st, 28th days. Blood lipid levels were measured at baseline and day 28.
Results: There was a persistent decrease in plasma glucose levels in the ranolazine treated animals during the study. Fasting plasma glucose levels were significantly lower in the ranolazine-treated group (206.3+12.74 mg/dl) compared with the vehicle group (437.8+34.03mg/dl) at 4 weeks. Ranolazine had a favourable effect on lipid profile when compared to the control (vehicle treated) animals.
Conclusions: Ranolazine improved glucose and lipid homeostasis in streptozotocin induced diabetic wistar rats. Further studies are needed to validate the findings and elucidate the exact mechanism.
Ning Y, Zhen W, Fu Z, Jiang J, Liu D, Belardinelli L, et al. Ranolazine increases beta-cell survival and improves glucose homeostasis in lowdose streptozotocin-induced diabetes in mice. J Pharmacol Exp Ther. 2011;337(1):50-8.
Dhalla AK, Yang M, Ning Y, Kahlig MK, Krause M, Rajamani S, et al. Luiz blockade of Na+ channels in pancreatic a-cells has antidiabetic effects. Diabetes. 2014;63:3545-56.
El Amrani FB, Guerra S, Aldasoro M. Anti-inflammatory and antioxidant effects of ranolazine in primary culture in primary cultured astrocytes. Crit Care. 2014;18(1)447-50.
McDaniel ML, Kwon G, Hill JR, Marshall CA, Corbett JA. Cytokine in Islet Inflammation and Diabetes. Exp Biol Med. 1996;221(1):24-32.
Zhang M, Xiao-Yan LV, Li J, Zhi-Gang XU, Li C. The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat. Exp Diabetes Res. 2008;2008:704045.
Prohp TP, Onoagbe IO, Joel P. Plasma glucose concentration and lipid profile in streptozotocin-induced diabetic rats treated with extracts of triplochiton scleroxylon K. Schum. International Journal of Analytical Pharmaceutical and Biomedical Sciences. 2012;1(1):22-9.
Dhanush KB, Suguna R, Satyanarayana ML. Serum insulin levels and lipid profiles of streptozotocin induced diabetic wistar rats. J Ind Vet Assoc. 2012;10(2):22-5.