In type 1 diabetes mellitus, the levels of insulin and C-peptide decrease at the periphery and in CNS. C-peptide potentiates the regulatory effects of insulin. We studied the effects of single and repeated (over 7 days) individual and combined nasal administration of C-peptide (10 μg/day) and insulin (20 μg/day) on activity of Akt kinase and kinase-3β-glycogen synthase (GSK3β), the components of 3-phosphoinositide pathway, in the hypothalamus of intact rats and rats with mild streptozotocin-induced type 1 diabetes mellitus. Phosphorylation of Akt kinase at Thr308 and Ser473 (stimulation) and GSK3β at Ser9 (inhibition) was evaluated. In diabetes, phosphorylation of Akt kinase and, to a lesser extent, GSK3β, is reduced. A single injection of insulin or C-peptide and insulin increased this process. Long-term combined treatment with C-peptide and insulin normalized activity of Akt kinase and GSK3β in diabetic rats, treatment with insulin alone produced less pronounced effect; monotherapy with C-peptide was ineffective. Intranasal co-administration of C-peptide and insulin effectively stimulates the insulin system in the hypothalamus that is weakened at diabetes mellitus type 1, which can be used in the treatment of this disease.
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 167, No. 3, pp. 324-329, March, 2019
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Derkach, K.V., Perminova, A.A., Buzanakov, D.M. et al. Intranasal Administration of Proinsulin C-Peptide Enhances the Stimulating Effect of Insulin on Insulin System Activity in the Hypothalamus of Diabetic Rats. Bull Exp Biol Med 167, 351–355 (2019). https://doi.org/10.1007/s10517-019-04525-w
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DOI: https://doi.org/10.1007/s10517-019-04525-w