The effect of plant-derived oleanolic acid on selected markers of lipid metabolism and insulin signalling pathway in streptozotocin-induced diabetic rats.

Abstract

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycaemia; this condition is caused by lack of insulin secretion (Type 1) and/or insulin resistance (Type 2). In diabetic patients; carbohydrate, protein and lipid metabolism is disturbed due to the lack of the body’s ability to utilise glucose efficiently. Management of type 1 diabetes involves insulin therapy which may be inconvenient for patients. Therefore alternative methods for management of type 1 diabetes involving medicinal products are being investigated. This study is aimed at investigating the effect of OA on markers of lipid metabolism and on proteins of the insulin signalling pathway in Type 1 diabetic rats as this plant product has anti-hyperglycaemic effects. Male Sprague-Dawley rats were divided into two groups (diabetic and normal). In both groups the rats were further divided into four groups and assigned to treatment as follows: vehicle, insulin, OA and OA plus insulin. Oral glucose tolerance test was performed in fasted and non-fasted diabetic rats for 2 hours. In acute studies the effect OA following treatment of rats was evaluated at 15, 30 and 60 minutes. In sub-chronic studies rats were treated daily for 14 days. OA did not improve glucose tolerance in diabetic rats after 2 hours of administration. However, it enhanced blood glucose lowering effect of insulin and this was statistically significant in fasted rats. In acute studies OA enhanced the effect of insulin in normal and diabetic animals as AKT phosphorylation was increased when insulin was used in combination with OA. OA reduced the expression and activity of HSL in liver tissue after 14 days of treatment in both normal and diabetic rats. In adipose tissue, OA reduced the expression of HSL in diabetic rats. However, OA alone did not reduce the activity of HSL but when it was combined with insulin, a reduction of HSL activity was observed. OA administration had no significant effect on TGA and HDL-c levels but significantly (p < 0.05) reduced total cholesterol and LDL-c in diabetic rats. It had no significant effect on total cholesterol, and increased LDL-c levels in normal rats. Serum AST and ALT levels in diabetic rats were reduced by OA administration but this reduction was not statistically significant. The results of this study suggest that OA enhances the hypoglycaemic effect of insulin, improves lipid profile and possesses hepatoprotective effects. Lastly, OA independently increases AKT phosphorylation and decreases HSL expression and activity.