C-peptide: new findings and therapeutic implications in diabetes

Clinical Physiology and Functional Imaging
J Wahren

Abstract

In contrast to earlier views, new data indicate that proinsulin C-peptide exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. C-peptide in nanomolar concentrations binds specifically to cell membranes, probably to a G-protein coupled receptor. Ca(2+)- and MAP-kinase dependent signalling pathways are activated, resulting in stimulation of Na(+), K(+)-ATPase and endothelial nitric oxide (NO) synthase, two enzyme systems known to be deficient in diabetes. C-peptide may also interact synergistically with insulin signal transduction. Studies in intact animals and in patients with type 1 diabetes have demonstrated multifaceted effects. Thus, C-peptide administration in streptozotocin-diabetic animals results in normalization of diabetes-induced glomerular hyperfiltration, reduction of urinary albumin excretion and diminished glomerular expansion. The former two effects have also been observed in type 1 diabetes patients given C-peptide in replacement dose for up to 3 months. Peripheral nerve function and structure are likewise influenced by C-peptide administration; sensory and motor nerve conduction velocities increase and nerve structural changes are diminished or reversed in diabe...Continue Reading

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