Prevention of Vascular and Neural Dysfunction in Diabetic Rats by C-Peptide

Abstract

C-peptide, a cleavage product from the processing of proinsulin to insulin, has been considered to possess little if any biological activity other than its participation in insulin synthesis. Injection of human C-peptide prevented or attenuated vascular and neural (electrophysiological) dysfunction and impaired Na+- and K+-dependent adenosine triphosphate activity in tissues of diabetic rats. Nonpolar amino acids in the midportion of the peptide were required for these biological effects. Synthetic reverse sequence (retro) and all-D-amino acid (enantio) C-peptides were equipotent to native C-peptide, which indicates that the effects of C-peptide on diabetic vascular and neural dysfunction were mediated by nonchiral interactions instead of stereospecific receptors or binding sites.

Fulminant type 1 diabetes as a high risk group for diabetic microangiopathy—a nationwide 5-year-study in Japan

“…C-peptide is considered to be a good marker of insulin secretion and has no biological activity of its own. However, over the last decade, several reports have suggested that C-peptide may exert a number of physiological effects, which are probably mediated by stimulation of Na + ,K + -ATPase and endothelial nitric oxide synthetase activities in several tissues [23]. In the early stage of type 1 diabetes, C-peptide replacement results in diminished UAE rate and ameliorates nerve dysfunction [24].…”

C-peptide stimulates ERK1/2 and JNK MAP kinases via activation of protein kinase C in human renal tubular cells

“…*p<0.05 vs control. A representative western blot image is shown in the upper panel of each graph Na + , K + -ATPase by this fragment [6,15,31,32], whereas scrambled C-peptide had no effect. In contrast to a previous study involving mouse endothelial cells [27], we did not observe an increase in p38 MAP kinase phosphorylation, which may be related to tissue-and speciesspecific differences.…”

Molecular basis for the insulinomimetic effects of C-peptide

“…No specific C-peptide receptor has been identified [7]. The introduction of a sensitive method, fluorescent correlation spectroscopy (FCS), has allowed specific C-peptide binding to human cells to be detected but the structure of the receptor is still not known.…”