Changes in Activity of Glycogen Synthase Kinase-3β in Transient Forebrain Ischemia in Rats against the Background of Intranasal Insulin Administrations.

Intranasal administration of insulin at a dose of 0.5 IU per rat 1 h before carotid artery occlusion and reperfusion prevented changes in the activity of signaling pathways in the brain. After 1-h reperfusion following 20-min occlusion of the carotid arteries, intranasal administration of insulin decreased the level of phosphorylation of glycogen synthase kinase-3β (GSK-3β) at the inhibitory site Ser9 in rats and returned it to the control level. After 3 days of reperfusion following 10-min occlusion of the carotid arteries, we observed inactivation of GSK-3β mediated by protein kinase B (Akt), which was supported by the similarity of their phosphorylation profiles. At the same time, intranasal administration of insulin before ischemia and over 3 days of reperfusion prevented accumulation of pGSK-3β (Ser9) and inactivation of the enzyme. It can be assumed that under conditions of transient ischemia and intranasal administration of insulin, GSK-3β participates in the regeneration processes. Therefore, the use of GSK-3β inhibitors is not recommended for this pathology.