PREVENTION OF VASCULAR AND NEURAL DYSFUNCTION IN DIABETIC RATS BY C-PEPTIDE

C-peptide, a cleavage product from the processing of proinsulin to ins ulin, 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 (electrophysiol ogical) dysfunction and impaired Na+- and K+-dependent adenosine triph osphate activity in tissues of diabetic rats. Nonpolar amino acids in the midportion of the peptide were required for these biological effec ts. Synthetic reverse sequence (retro) and all-D-amino acid (enantio) C-peptides were equipotent to native C-peptide, which indicates that t he effects of C-peptide on diabetic vascular and neural dysfunction we re mediated by nonchiral interactions instead of stereospecific recept ors or binding sites.