Ernst-Friedrich-Pfeiffer Memorial Lecture. 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 Cpeptide 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 Ca2dependent 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.