Abstract

Co-administration of high-fat diet (HFD) and Streptozotocin (STZ) has been reported to induce insulin resistance (IR) in Wistar rats. Peroxisome proliferator-activated receptors-gamma (PPARγ) agonist drugs such as pioglitazone (PIO) have been used to effectively treat various metabolic-related diseases. Tis study aimed to determine the role of pioglitazone on hippocampal structure and function in rat model of type 2 diabetes mellitus. Twenty-four male Wistar rats (200 g ± 20) were divided into four groups (control, HFD+STZ, PIO, HFD+STZ+PIO). The animals were fed on high-fat diet for 12 weeks concurrently with streptozotocin injection (30 mg/kg bw i.p) for 5 consecutive days to induce insulin resistance form of type 2 diabetes mellitus. Pioglitazone (20 mg/kg bw, orally) was administered for 2 weeks. After the administration period, neurobehavioural evaluation, oxidative stress markers, indices for insulin resistance and histological changes were assessed. Co-administration of high fat diet and streptozotocin significantly increased blood glucose and insulin levels alongside increased MDA and decreased GSH level in HFD+STZ compared to control. However, pioglitazone significantly reduced blood glucose and insulin levels, decreased MDA and increased GSH levels in HFD+STZ+PIO. Histological assessment also demonstrated severe series of cellular damages in HFD+STZ. On the contrary, pioglitazone potentiates its neuroprotective role via presence of mild neuronal damages in the hippocampus of HFD+STZ+PIO. In conclusion, Pioglitazone has potentiated its ameliorative role on hippocampal degeneration by improving cognitive function in high-fat diet and streptozotocin-induced type 2 diabetes mellitus via its activities on neurobehavioural deficits, oxidative stress and hippocampal cellular architecture.