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Science 25 July 1997:
Vol. 277. no. 5325, pp. 563 - 566
DOI: 10.1126/science.277.5325.563
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Reports

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

Y. Ido, A. Vindigni, K. Chang, L. Stramm, R. Chance, W. F. Heath, R. D. DiMarchi, E. Di Cera, J. R. Williamson *

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.

Y. Ido, K. Chang, J. R. Williamson, Department of Pathology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
A. Vindigni and E. Di Cera, Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
L. Stramm and R. Chance, Endocrine Division, Lilly Research Labs, Lilly Corporate Center, Indianapolis, IN 46285, USA.
W. F. Heath and R. D. DiMarchi, Research Technologies and Protein, Lilly Research Labs, Lilly Corporate Center, Indianapolis, IN 46285, USA.
*   To whom correspondence should be addressed.

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