Effect of sitagliptin on the working memory and reference memory in type 2 diabetic Sprague-Dawley rats: possible role of adiponectin receptors 1.

Type 2 diabetes mellitus (DM) is associated with increased incidence of behavioral changes and memory loss. Memory loss could be caused by Alzheimer's disease (AD) and vascular dementia (VaD). So, we aimed to investigate the effect of sitagliptin in improving the working and reference memories in diabetic rats. Thirty six male Sprague-Dawley rats divided equally (n=12) into three groups: control, type 2 DM and type 2 DM treated with DPP-4 inhibitor (sitagliptin) for one month (10 mg/kg) orally. Working memory and reference memory were assessed by using the holeboard memory test. In all rats, serum glucose, insulin, adiponectin, total cholesterol (TC), TG, low (LDL) and high (HDL) density lipoprotein with calculation of the homeostasis model of assessment-insulin resistance index (HOMA-IR) and atherogenic index. The hypothalamus was separated for determination of the acetylcholine level and adiponectin receptors 1 (Adipo R1) m-RNA expression. Type 2 diabetic rats exhibited a significant decrease in both working and reference memories, with increased glucose, insulin and HOMA-IR. The adiponectin level, acetylcholine content of the hypothalamus and Adipo R1 m-RNA expression were significantly reduced. Treatment with sitagliptin significantly improved the working and reference memories with significant reduction in the glucose, insulin and HOMA-IR. Moreover, sitagliptin increased significantly the acetylcholine content of the hypothalamus and Adipo R1 expression. In conclusion, sitagliptin might improve the cognitive function of the diabetic rats and the hypothalamic acetylcholine level possibly through increased AdipoR1 expression.