Intranasal Administration of Proinsulin C-Peptide Enhances the Stimulating Effect of Insulin on Insulin System Activity in the Hypothalamus of Diabetic Rats
- 作者: Derkach K.1, Perminova A.1, Buzanakov D.1, Shpakov A.1
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隶属关系:
- Laboratory of Molecular Endocrinology and Neurochemistry, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Science
- 期: 卷 167, 编号 3 (2019)
- 页面: 351-355
- 栏目: Article
- URL: https://journals.rcsi.science/0007-4888/article/view/241694
- DOI: https://doi.org/10.1007/s10517-019-04525-w
- ID: 241694
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详细
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.
作者简介
K. Derkach
Laboratory of Molecular Endocrinology and Neurochemistry, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Science
Email: alex_shpakov@list.ru
俄罗斯联邦, St. Petersburg
A. Perminova
Laboratory of Molecular Endocrinology and Neurochemistry, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Science
Email: alex_shpakov@list.ru
俄罗斯联邦, St. Petersburg
D. Buzanakov
Laboratory of Molecular Endocrinology and Neurochemistry, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Science
Email: alex_shpakov@list.ru
俄罗斯联邦, St. Petersburg
A. Shpakov
Laboratory of Molecular Endocrinology and Neurochemistry, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Science
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Email: alex_shpakov@list.ru
俄罗斯联邦, St. Petersburg
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