Effects of metformin, combined use of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors on serum nesfatin-1 levels, some vitamins and biochemical parameters in streptozotocin-nicotinamide induced diabetic rats

Objective: In this study, we aimed to investigate the effects of metformin administration and the combined use of DPP-4 enzyme inhibitors sitagliptin and omarigliptin with metformin on some biochemical and anthropometric parameters in rats with streptozotocin (STZ)- nicotinamide (NA) induced diabetes mellitus. Material and Methods: 50 male Wistar-Albino rats aged 3-4 months and weighing 200-230 g were divided into five groups with ten experimental animals in each group. Except for the 1st group, the healthy control (HC) group, rats in the other four groups were administered STZ-NA. Fasting blood glucose levels were measured 72 hours after STZ-NA administration, and those above 150 mg/dL were considered diabetes and included in the study. Group 2 diabetic control (DC) rats were treated with saline, group 3 with metformin, group 4 with metformin+sitagliptin, and group 5 with metformin+omarigliptin by oral gavage for 28 days. The rats' fasting blood glucose levels, weight, and height were measured at the beginning of each week. At the end of the experiment, Nesfatin-1, vitamin B12, 25-dihydroxy vitamin D, and Insulin levels in serum were determined by ELISA kits in ELISA device; alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase, lipase, total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and very low density lipoprotein (VLDL) levels were determined spectrophotometrically by autoanalyzer. Results: In terms of fasting blood glucose values, glucose levels of diabetic groups were found to be higher than the HC group (p<0.001). No statistical difference was found between the fasting blood glucose values of the diabetic groups (p>0.05). Regarding weight, BMI, and Lee index, the values of the diabetic groups were lower than those of the HC group (p<0.05). No difference was found between the diabetic groups regarding weight, BMI, and Lee index (p>0.05). Also there was no difference between the groups in terms of vitamin B12, 25-dihydroxy vitamin D and insulin values (p>0.05). Nesfatin-1 values of the 5th group were higher than the 2nd group (p<0.05). ALT values of group 2 and group 5 were higher than the ALT values of the HC group (p<0.05). AST values of the 2nd group were higher than the AST values of the HC group (p<0.05). The amylase values of the diabetic groups were lower than those of the HC group (p<0.05), and the lipase values of the 2nd and 5th groups were higher than those of the HC group (p<0.05). Total cholesterol values of the 2nd group, 3rd group, and 5th group were lower than those of the HC group (p<0.05). Triglyceride values of the 2nd and 4th groups were higher than those of the HC groups (p<0.05). HDL values of the 2nd group were lower than those of the HC group (p<0.05), and VLDL values of the 2nd and 4th groups were higher than those of the HC group (p<0.05). LDL values of the HC group were higher than those of the 2nd, 3rd, and 5th groups (p<0.05). Conclusion: No significant difference was found between the different drug therapies applied in diabetic groups on the results in terms of the parameters examined. However, although not statistically significant, it was observed that sitagliptin was the most hepatoprotective drug, and omarigliptin was the most effective drug in improving lipid profiles (p>0.05). In addition, the use of omarigliptin caused a significant increase in Nesfatin-1 levels (p<0.05). Keywords: Diabetes, Metformin, Nesfatin-1, Nicotinamide, Omarigliptin, Rat, Sitagliptin, Streptozotocin