Prevention of vascular and neural dysfunction in diabetic rats by C-peptide.
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.
Ido
Y
Y
Department of Pathology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Vindigni
A
A
Chang
K
K
Stramm
L
L
Chance
R
R
Heath
W F
WF
DiMarchi
R D
RD
Di Cera
E
E
Williamson
J R
JR
D000595:Amino Acid Sequence; D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D002199:Capillary Permeability / Q000187:drug effects; D002942:Circular Dichroism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D003929:Diabetic Neuropathies / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009431:Neural Conduction / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D017433:Protein Structure, Secondary; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013237:Stereoisomerism
D001786:Blood Glucose; D002096:C-Peptide; D010446:Peptide Fragments; D000254:Sodium-Potassium-Exchanging ATPase