Effect of Intranasally Administered Insulin on Metabolic Parameters and Inflammation Factors in Control and Diabetic Rats under Conditions of Cerebral Ischemia and Reperfusion

The search for natural biologically active substances that have a neuroprotective effect on cerebral ischemia-reperfusion is one of the urgent problems of modern neuroscience and medicine. Intranasally administered insulin (IAI) has a pronounced restorative effect on various neurodegenerative diseases, but the mechanisms of its action and therapeutic effects in cerebral ischemia have not been studied well, including in type 2 diabetes mellitus (DM2), which increases the risk of cerebrovascular dysfunction. The aim of the work was to study the effect of IAI on metabolic parameters and inflammatory factors in male rats with DM2 subjected to the two-vessel ischemia and prolonged forebrain reperfusion, in comparison with non-diabetic animals. A long-term high-fat diet with an injection of a low dose of streptozotocin (25 mg/kg) to rats was used to induce DM2, and a model of the global forebrain two-vessel ischemia induced by occlusion of both common carotids with prolonged reperfusion (IR) for 7 days was used to study cerebral ischemia. Two hours after the end of ischemia, rats were treated with IAI at a dose of 0.5 or 2.0 IU/rat, after which the drug was administered in the same doses daily for 7 subsequent days. It was found that IAI prevents body weight loss in both nondiabetic and diabetic rats that underwent IR, and also increases the total cholesterol level and the proportion of epididymal fat in rats without DM2 after IR. In DM2 rats that underwent IR, IAI in the explored doses reduces the level of postprandial glucose and insulin content in the blood, which indicates an improvement of glucose tolerance, and also reduces the levels of inflammatory factors in the blood – C-reactive protein (at a dose of 0.5 IU/rat/day) and tumor necrosis factor-α (in a dose of 2 IU/rat/day), which reveals its anti-inflammatory potential. Thus, the course treatment with IAI after induction of cerebral ischemia followed by reperfusion leads to an improvement of metabolic parameters and weakens inflammatory reactions in rats with DM2, which may be in demand in the correction of ischemic stroke in patients with DM2.