A positive effect of intranasal insulin on spatial memory in rats with neonatal diabetes mellitus

Abstract

Type 2 diabetes mellitus (T2DM) is associated with cognitive impairments. However, their causal factors and the approaches to be used in their treatment have not been fully clarified and further study is needed. The aim of this work was to study the effect of intranasal insulin (I-I) on cognitive functions in rats with experimental T2DM. Neonatal rats (5 days old) were treated with an intraperitoneal (i.p.) administration of a single dose of streptozotocin (STZ) (80 mg/kg i.p.) which in adult animals leads to impairment of glucose tolerance and mild hyperglycemia, typical of T2DM. The insulin receptor binding in the synaptosomal and liver membranes was evaluated with [ 125 I]-insulin, and the insulin receptor substrate 2 (IRS2) expression in the brain was estimated by RT-PCR. Daily I-I (0.48 IU/day) or placebo were delivered to diabetic and non-diabetic rats during a week before and the 39 days of cognition experiments. Spatial memory and learning were studied in a Morris water-maze (MWM) test. The MWM test showed that, in the case of diabetic rats, the latent period for finding the platform (escape latency) and the swimming path length were increased, and the number of annulus crossings decreased compared with control (P<0.05). I-I normalized cognitive functions in diabetic rats but had no effect on those of non-diabetic animals. Specific insulin binding in the liver of diabetic rats was decreased, indicating peripheral insulin resistance, but changed very little in the brain. In the hypothalamus of diabetic rats, but not in the cortex and the olfactory bulbs, the expression of IRS2 was reduced by 68% compared with control and was restored after I-I delivery. Rats with neonatal T2DM had cognitive deficit likely associated with impaired IRS2-mediated signaling pathways in the diabetic brain and eliminated by I-I treatment.

Effect of Glycemic Control Using Different Antidiabetic Drugs on Cognitive Functions in Experimentally-Induced Type 2DM: A Comparative Study

“…Compared with Diabetic group, the Diabetic+ Insulin and Diabetic+ Janumet groups exhibited a significant elevation in serum insulin levels in the current study. This result corroborated the preceding findings (18,23,24) . However, the Diabetic+ Janumet group exhibited a significant elevation in serum insulin levels compared with Diabetic+ Insulin group.…”

Antidiabetic Effect of Galantamine: Novel Effect for a Known Centrally Acting Drug

“…As a support, Chistyakova et al . [ 34 ] owed the cognitive deficit in rats with neonatal T2DM to the reported low brain insulin concentration and impaired insulin receptor substrate-2-mediated signaling pathways in the brain.…”

Alterations of Hormone-Sensitive Adenylyl Cyclase System in the Tissues of Rats with Long-Term Streptozotocin Diabetes and the Influence of Intranasal Insulin

“…We showed that the 135-day therapy with I-I prevents the decline of AC stimulation induced by PACAP-38 in the diabetic brain. us, the ability of I-I to restore AC signaling pathways regulated by PACAP-38 and some biogenic amines may be one of the main mechanisms of positive in�uence of I-I on the impaired CNS functions in human and experimental DM [16,24,32]. e AC effect of dopamine, contrary to the other investigated hormones, did not change in the diabetic brain.…”