title: [Pleiotropic action of proinsulin C-peptide].
abstract: Proinsulin C-peptide, released in equimolar amounts with insulin by pancreatic β cells, since its discovery in 1967 has been thought to be devoid of biological functions apart from correct insulin processing and formation of disulfide bonds between A and B chains. However, in the last two decades research has brought a substantial amount of data indicating a crucial role of C-peptide in regulating various processes in different types of cells and organs. C-peptide acts presumably via either G-protein-coupled receptor or directly inside the cell, after being internalized. However, a receptor binding this peptide has not been identified yet. This peptide ameliorates pathological changes induced by type 1 diabetes mellitus, including glomerular hyperfiltration, vessel endothelium inflammation and neuron demyelinization. In diabetic patients and diabetic animal models, C-peptide substitution in physiological doses improves the functional and structural properties of peripheral neurons and protects against hyperglycemia-induced apoptosis, promoting neuronal development, regeneration and cell survival. Moreover, it affects glycogen synthesis in skeletal muscles. In vitro C-peptide promotes disaggregation of insulin oligomers, thus enhancing its bioavailability and effects on metabolism. There are controversies concerning the biological action of C-peptide, particularly with respect to its effect on Na⁺/K⁺-ATPase activity. Surprisingly, the excess of circulating peptide associated with diabetes type 2 contributes to atherosclerosis development. In view of these observations, long-term, large-scale clinical investigations using C-peptide physiological doses need to be conducted in order to determine safety and health outcomes of long-term administration of C-peptide to diabetic patients.
authors.affiliation: Zakład Regulacji Metabolizmu, Instytut Biochemii, Wydział Biologii, Uniwersytet Warszawski, ul. I. Miecznikowa 1, 02-096 Warszawa. musarek@biol.uw.edu.pl
authors.forename: Michał
authors.initials: M
authors.lastname: Usarek
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Bryła
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D050197:Atherosclerosis / Q000209:etiology; D002096:C-Peptide / Q000378:metabolism* / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000517:prevention & control; D003929:Diabetic Neuropathies / Q000378:metabolism / Q000517:prevention & control; D004195:Disease Models, Animal; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D017933:Peripheral Nervous System / Q000187:drug effects / Q000378:metabolism
chemical_list: D002096:C-Peptide; D006003:Glycogen