Abstract

EFFECT OF IBUTILIDE AND SOTALOL IN STREPTOZOTOCIN AND NICOTINAMIDE INDUCED DIABETES MELLITUS IN RAT

Pavithra P.*, Dinesh Babu K. and Kavimani S.

ABSTRACT

Diabetes mellitus is a serious complex chronic condition that is a major source of ill health worldwide. This metabolic disorder is characterized by hyperglycemia and disturbances of carbohydrate, protein and fat metabolisms, secondary to an absolute or relative lack of the hormone insulin. Reasons for this include increase in sedentary lifestyle, consumption of energy rich diet, obesity, etc. Streptozotocin, a glucosamine-nitrosurea compound from Streptomyces achromogens that is used clinically as a chemotherapeutic agent in the treatment of pancreatic β cell carcinoma. It induces diabetes by free radical generation, which causes a massive reduction of insulin secreting beta-cells of the islets of Langerhans, resulting in a decrease in endogenous insulin release. The anti-diabetogenic effect of nicotinamide may be due, in part to increase in the pool size of NAD++ in beta cells. NAD++ is the principal metabolite of nicotinamide. It appears that the pool size of NAD++ in beta-cells may occur via oxidative stress. Nicotinamide is an inhibitor of PARP. Nicotiamide by the above mechanism opposes the effect of streptozotocin, helps in partial destruction of beta cells and helps in the development of type-2 diabetes mellitus. Release of insulin requires closure of potassium channels and subsequent opening of calcium channels in beta cells of pancreas. As we known that both Ibutilide and Sotalol has an ability to block ATP-sensitive potassium channels. Due to blockade of this channels, those drugs act as insulin secretogogues and exhibit anti-hyperglycemic activity. In diabetes mellitus there will be significant changes in serum lipid profile may lead to hyperlipidemia characterized by the elevation of total cholesterol, triglycerides and LDL levels. However, there was a decreased levels of HDL. In the present study, treatment with Ibutilide and Sotalol significantly reversed dyslipidemia by the significant decrease in TC, TG and LDL coupled to increase in HDL. A histopathology study of pancreas shows the partial destruction of the pancreatic cells in DM control animals. The histopathology study of Ibutilide and Sotalol as well as Glibenclamide treated animals showed restoration of pancreatic cells. Hence, Potassium channel blockers such as Ibutilide and Sotalol may be used concurrently with other oral antidiabetic drugs for the treatment of type-II Diabetes Mellitus.

Keywords: Diabetes mellitus, Ibutilide, Sotalol, Streptozotocin, Nicotinamide, Potassium channel.