Effect of Intranasal Insulin on Metabolic Parameters and Inflammation Factors in Diabetic Rats Exposed to Cerebral Ischemia-Reperfusion

The search for natural biologically active substances havinga neuroprotective effect against cerebral ischemia-reperfusion injuryis one of the major priorities of modern neuroscience and medicine. Intranasalinsulin (INI) exerts a pronounced restorative effect on variousneurodegenerative diseases, but the mechanisms of its action andits therapeutic effects in cerebral ischemia have not been wellstudied, including in type 2 diabetes mellitus (DM2) which increasesthe risk of cerebrovascular dysfunction. The aim of the work wasto study the effect of INI on metabolic parameters and inflammatoryfactors in male Wistar rats with DM2, exposed to cerebral ischemia,as compared to nondiabetic animals. DM2 was induced by a combinationof high-fat diet and low-dose (25 mg/kg) streptozotocin administration. Cerebralischemia was studied in a rat model of global forebrain ischemia-reperfusion(IR) injury induced by occlusion of both common carotid arteries,followed by a 7-day reperfusion. Two h after the end of ischemicexposure, the rats were treated with INI at a dose of 0.5 or 2.0IU/rat, after which the drug was administered at the same dose,once a day, for the following 7 days. INI was found to prevent bodyweight loss in both nondiabetic and DM2 IR-exposed rats, while elevatingplasma total cholesterol levels and epididymal fat fraction in IR-exposednondiabetic animals only. In IR-exposed DM2 rats, INI (at both dosesused) reduced postprandial plasma levels of glucose and insulin,indicative of improved glucose tolerance, as well as plasma levelsof inflammatory factors, C-reactive protein (at a dose of 0.5 IU/rat/day),and tumor necrosis factor-α (at a dose of 2 IU/rat/day), indicativeof its anti-inflammatory potential. Thus, a post-IR course treatmentwith INI improves metabolic parameters and abates inflammatory responsesin DM2 rats, which may be in high demand when correcting ischemic strokein patients with DM2.