Evaluation the Effect of Chronic Obestatin Therapy on the Serum Glucose, Insulin And Lipid Levels in Type 2 Diabetic Rats

Background: Diabetes mellitus (DM) is one of the most common health disorders, which has become increasingly common in recent years. Type 2 diabetes affects about 90-95% of all diabetic patients, and is often associated with obesity and insulin resistance in most patients. The medical treatment aims to reduce insulin resistance and increase the production of insulin by pancreatic β-cells. Obestatin is a new hormone encoded by the Preghrelin gene. Obestatin is an anorexic hormone that reduces food intake. It has also been shown to play an important role in regulating glucose and lipid levels in the blood. Study Aim: Our study aims to evaluate the therapeutic benefit of obestatin in rats with experimental type 2 diabetes in reducing blood glucose and improving insulin levels, and its effect on insulin resistance, TG, TC and pancreatic β-cell survival. Methods: A total of 30 male Wister rats (150 -200g) were randomly divided into three groups: group I (control group), group II (T2DM group) induced by administration fructose solution 10% for 14 days, and single injection IP of streptozotocin (STZ) (35 mg/Kg), group III (T2DM treated with obestatin) (25 μg/kg) IP twice daily for 30 days. Blood samples were collected at the end of the experiment by terminal intracardiac sampling for bioassays to estimate fasting glucose, insulin, triglyceride (TG), total cholesterol (TC), and assessment of HOMA-IR. Body weight was also measured. Mean ± STD was calculated. The statistical significance of differences across the groups was determined by one-way ANOVA followed by a post Hoc Turkey’s test. The differences were considered significant at 0.05˃P. Results: After 30 days of obestatin treatment, the diabetic group showed a significant increase in glucose, TG, TC and HOMA-IR values and a significant decrease in insulin levels compared to the control group. In comparison, the obestatin-treated group of diabetic patients showed a significant decrease in glucose, TG and TC levels, with a slight increase in the insulin level compared to the diabetic group. In addition, the histological study (H&E) of isolated pancreatic tissue from the second group showed deformed, shrunken Langerhans islets with significant loss of their β- cells, and some cells with vacuolated cytoplasm. Moreover, the histological features of the treatment group were somewhat similar to those of the control group. Conclusion: The results of our study showed the efficacy of obestatin as a treatment in reducing the levels of all glucose, triglycerides and total cholesterol in the blood to normal limits in induced experimental rats with type 2 diabetes. Moreover, the improvement of insulin levels in the blood, and the results of the histological study showed an improvement in the size of the islet and an increase in the number of β-cells. Thus, obestatin can be used as a promising target in the treatment of metabolic diseases such as diabetes and obesity.