Does C-peptide have a physiological role?

Short-term administration of physiological amounts of C-peptide to patients with insulin-dependent diabetes was found to reduce the glomerular hyperfiltration in these patients as well as augment whole body glucose utilization. It could also be shown that C-peptide administration increases blood flow, oxygen uptake and capillary diffusion capacity of exercising forearm muscle in IDDM patients, probably by increasing capillary recruitment in the working muscle. Studies under in vitro conditions have shown that C-peptide stimulates glucose transport in skeletal muscle with its maximal effect within the physiological concentration range. The findings in a clinical study in which IDDM patients were given C-peptide and insulin or insulin alone for 4 weeks in a double-blind randomized study design, indicate that C-peptide improves renal function by reducing urinary albumin excretion and glomerular filtration, decreases blood retinal barrier leakage and improves metabolic control. Preliminary findings suggest that C-peptide administration on a short-term basis (3h) may ameliorate autonomic neuropathy by restoring to near normal the heart rate variability in response to expiration and inspiration. Insight into a possible mechanism of action of C-peptide is provided by the finding that C-peptide stimulates Na+K(+)-ATPase activity in renal tubular segments. In conclusion, the present results suggest that, contrary to the prevailing view, C-peptide possesses important physiological effects.