Insulin-dependent diabetic (
IDDM) patients present significantly altered Na,K-
ATPase activity in several organs, including kidney. Particularly in kidney tubule, Na,K-
ATPase alteration occurs together with changes in glomerular filtration rate, the first step of
IDDM-induced
renal failure. The latter is a major cause of morbidity and mortality in
IDDM patients. The
C-peptide of
proinsulin is important for the biosynthesis of
insulin but has for a long time been considered to be biologically inert. Recent studies have demonstrated that replacement of
C-peptide to normal physiological concentrations in
IDDM patients either on a short-term basis (1-3 hours) or on a prolonged administration (1-3 months) was accompanied by improvements in renal glomerular and tubular function. Animal studies have shown that most of the renal tubular effects of
C-peptide may in part be explained by its ability to stimulate Na,K-
ATPase activity. In conclusion, these combined findings indicate that
C-peptide is a biologically active
hormone. The possibility that
C-peptide therapy in
IDDM patients may be beneficial should be considered. The present review focuses on: 1) Making a point about
C-peptide-induced tubular effects on the basis of clinical and experimental experiments, and 2) precising the molecular mechanisms involved in
C-peptide-induced tubular Na,K-
ATPase effects.