C-PEPTIDE: STRUCTURE, FUNCTIONS AND NOLECULAR MECHANISMS OF ACTION
A.O. Shpakov,1 O.K. Granstrem 2
1 Sechenov Institute Evolutionary Physiology and Biochemistry of RAS and 2 CJSC "Pharm-Holding", St. Petersburg;
e-mail: alex_shpakov@list.ru
C-peptide, which is formed during the biosynthesis of insulin, for a long time considered as a biologically inactive substance. But in the last years there are convincing evidences
that the deficit of C-peptide in type 1 diabetes mellitus (DM) or its excess in DM2 lead to the development of disorders in the cardiovascular, nervous, excretory, and other systems
of organism. It is shown that C-peptide in the physiological concentrations has anti-inflammatory, immunomodulatory and neuroprotective effects, so that it and its synthetic analogs
can be widely used to treat diabetic patients and to prevent DM complications diabetes. To effectively use C-peptide in medicine it is necessary to study its structural-functional
organization and the molecular mechanisms of regulatory action of C-peptide on the fundamental cellular processes. Is established that C-peptide coupled with Gi/o
protein-coupled receptors of the serpentine type regulates the functional activity of many intracellular signaling pathways, which include phospholipase Ñβ, different forms
of protein kinase Ñ, phosphatidylinositol 3-kinases and mitogen-activated protein kinases, endothelial NO-synthase, Na+/K+-ATPase, a wide range of
transcription factors and nuclear receptors. C-peptide controls the stability of the insulin hexamer complexes and, thus, influences on the activity of insulin and insulin-regulated
signaling pathways. The present review is devoted to analysis of the current state of the problem of structural-functional organization of C-peptide and its mechanism of action on
the intracellular signaling pathways, as well as the prospects for the use of C-peptide in the fundamental biology and clinical medicine.
Key words: Na+/K+-ATPase, inflammation, heterotrimeric G protein, diabetes, immunomodulator, insulin, mitogen-activated
protein kinase, C-peptide, NO-synthase, factor NF-κB, phospholipase C
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