New results present C-peptide as a biologically active
peptide hormone in its own right. Although C-peptide is
formed from proinsulin and cosecreted with insulin, it is a
separate entity with biochemical and physiological characteristics
that differ from those of insulin. There is direct
evidence of stereospecific binding of C-peptide to a
cell surface receptor, which is different from those for insulin
and other related hormones. The C-peptide binding
site is most likely a G–protein–coupled receptor. The association
constant for C-peptide binding is approximately
3 × 109M-1. Saturation of the binding occurs already at a
concentration of about 1 nM, which explains why C-peptide
effects are not observed in healthy subjects. Binding of C-peptide
results in activation of Ca2+ and MAPK-dependent
pathways and stimulation of Na+,K+-ATPase and eNOS
activities. The latter 2 enzymes are both deficient in several
tissues in type 1 diabetes. There is some evidence that
C-peptide, and insulin may interact synergistically on the
insulin signaling pathway. Clinical evidence suggests that
replacement of C-peptide, together with regular insulin
therapy, may be beneficial in patients with type 1 diabetes
and serve to retard or prevent the development of long-term
complications.
