combined metformin and insulin therapy improves neurocognitive dysfunction in type 2 diabetic rat model via anti-inflammatory and antioxidant mechanisms

Introduction: improper glycemic control is associated with diabetic cognitive dysfunction. several studies have confirmed the neuroprotective effects of metformin and insulin. this study aimed to investigate the effects of metformin and/or insulin therapy on neurocognitive functions in a type 2 diabetes mellitus (t2dm) rat model.methods: fifty adult male wistar rats were used in this study and had free access to water and a normal chow diet. after an acclimatization period, 10 rats were kept on a normal chow diet and considered as the control group. t2dm was induced in the other 40 rats by a high-fat diet and low-dose streptozotocin method. then, diabetic rats were randomly allocated into 4 equal groups: non-treated diabetic group; metformin-treated diabetic group (treated with metformin 250 mg/kg/day for 6 weeks); insulin-treated diabetic group (treated with nph insulin 40 u/kg for 6 weeks); and metformin and insulin-treated diabetic group. neurocognitive functions were assessed by footprint assay, y-maze, open field test, and morris water maze. glycaemic profile, serum levels of amyloid a, interleukin-18, and nuclear factor-kappa b were analyzed. brain malondialdehyde and total antioxidant capacity were measured. a histopathological examination of the frontal lobe was performed.results: treatment with metformin and/or insulin significantly improved the impaired neurocognitive dysfunction, brain oxidative stress, changes in biochemical parameters, and the associated histopathological changes in the frontal cortex of diabetic rats. the combined therapy showed a better effect than either monotherapy alone.conclusion: metformin and insulin therapy may be valuable for the prevention of neurocognitive dysfunction in t2dm.