Protective effects of triterpenoid betulin on type 2 diabetes mellitus in rats

Abstract Type 2 diabetes mellitus (T2DM) is a complex chronic metabolic disease characterized by long-term hyperglycemia, which is, in turn, resulted from the impaired insulin signaling caused by a combination of insulin resistance or inadequate insulin production. Prevalence and incidence of T2DM are increasing dramatically across the world, and it is accompanied with severe complications and premature mortality of patients with diabetes. Given the fact that synthetic drugs have disadvantages in view of the side effects, the implementation of naturally occurring compounds for diabetes treatment may be a promising alternative. Betulin is a naturally occurring triterpenoid which has been shown to possess the ability of altering body lipids and exert hypoglycemic and hepatoprotective effects. It is suggested that the application of betulin in T2DM may have a favorable effect to ease the severity of diabetic complications. Thus, the aim of the present study was to assess biological effects of betulin in T2DM conditions. Diabetes-induced rats were administered with two different doses of betulin for 28 consecutive days. It was shown that long-term administration of betulin at the doses of 50 and 100 mg/kg/day to the rats prevented diabetes-associated changes in a body weight of the animals, significantly reversed insulin resistance and abolished the impairment of glucose metabolism. It was accompanied with the dose-dependent normalization of serum lipid contents. Histopathological changes and structural abnormalities in the liver of diabetics were restored by the administration of betulin. Also, betulin was able to restrain systemic inflammation detected in diabetic animals according to the altered levels of serum TNFα. Thus, the results obtained in the current study were found to be in agreement with earlier findings on beneficial effects of betulin in conditions pathogenetically close to T2DM. We hypothesized that the ability of betulin to restrain systemic inflammation and to normalize the lipid metabolism can explain improved insulin resistance and glycemic control and it can provide a possible mechanism for the beneficial antidiabetic effects of betulin.