New Aspects of C-Peptide Physiology

C-peptide is co-secreted with insulin and has generally been considered not to possess biological activity. However, several recent studies during the last five years have demonstrated that administration of C-peptide in physiological amounts to type 1 diabetes (IDDM) patients on a short term basis (1 - 3 h) results in decreased glomerular hyperfiltration, augmented glucose utilization and improved autonomic nerve function. More prolonged administration (1 - 3 months) of C-peptide to IDDM patients is accompanied by improvements in both renal function (diminished microalbuminuria) and autonomic and sensory nerve function. Both in vitro and in vivo data indicate that C-peptide may have a role in the regulation of insulin secretion. C-peptide's mechanism of action is not known but it may be related to its ability to stimulate Na⁺,K⁺-ATPase, activity, probably by activating a receptor coupled to a pertussis toxin-sensitive G-protein with subsequent activation of Ca²⁺-dependent intracellular signaling pathways. In conclusion, the 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.

Key words

Diabetes mellitus - IDDM - Glomerular hyperfiltration - Neuropathy - Insulin secretion - Microalbuminuria - Na⁺,K⁺-ATPase