Immunohistochemical, apoptotic and biochemical changes by dipeptidyl peptidase-4 inhibitor-sitagliptin in type-2...

Diabetes is a major public health problem that is rapidly increasing in prevalence. In this study, the effects of sitagliptin, a dipeptidyl peptidase-4 inhibitor, were examined on newborn diabetic rat model.

Wistar albino newborn rats were divided into control (Ctrl), sitagliptin (Sit), diabetic and diabetic+Sit groups. On the second day after the birth, 100mg/kg streptozotocin (STZ) was administered intraperitoneally in a single dose to induce type-2 diabetes in rats. The Sit and diabetic+Sit groups were administered sitagliptin (1.5mg/kg subcutaneous) as of the day 5 for 15 days. The pancreas sections were stained with insulin (INS), glucagon (GLU), somatostatin (SS), glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-1 receptor (GLP-1R) antibodies by the streptavidin-biotin peroxidase technique. The TUNEL method for apoptosis and biochemical analysis were performed in the pancreas and serum, respectively.

Body weight and blood glucose levels showed significant differences among all groups on days 11 and 20. In diabetic rats following treatment with sitagliptin, the area percentage of INS immunopositive cells increased while the area percentage of SS immunopositive cells decreased, insignificantly. A significant increase was observed on the area percentage of GLU, GLP-1 and GLP-1R immunopositive cells in the diabetic+Sit group when compared to the diabetic group. The area percentage of apoptotic cells was the same among all groups. While serum glutathione and malondialdehyde levels demonstrated insignificant alterations, the catalase and superoxide dismutase activity significantly changed among four groups.

According to our findings, sitagliptin may be a useful therapeutic agent to a certain extent of type-2 diabetic condition.