Intranasal Administration of Proinsulin C-Peptide Enhances the Stimulating Effect of Insulin on Insulin System Activity in the Hypothalamus of Diabetic Rats

• Published in: Bulletin of experimental biology and medicine 2019-07, Vol.167 (3), p.351-355
• Main Authors: Derkach, K. V., Perminova, A. A., Buzanakov, D. M., Shpakov, A. O.
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; AKT protein; Animals; Biomedical and Life Sciences; Biomedicine; C-Peptide - administration & dosage; C-Peptide - pharmacology; Cell Biology; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Experimental - drug therapy; Drug Synergism; Ethylenediaminetetraacetic acid; Glucose; Glycemic Index - drug effects; Glycogen; Glycogen synthase kinase 3; Glycogen Synthase Kinase 3 beta - metabolism; Hypothalamus; Hypothalamus - metabolism; Insulin; Insulin - pharmacology; Internal Medicine; Intranasal administration; Laboratory Medicine; Male; Pathology; Peptides; Phosphatidylinositols - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Wistar; Rodents; Streptozocin; Synthesis; Type 1 diabetes; Weight Loss - drug effects
• ISSN: 0007-4888; 1573-8221
• DOI: 10.1007/s10517-019-04525-w

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 Thr 308 and Ser 473 (stimulation) and GSK3β at Ser 9 (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.