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C‐peptide: new findings and therapeutic implications in diabetes
Author(s) -
Wahren John
Publication year - 2004
Publication title -
clinical physiology and functional imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.608
H-Index - 67
eISSN - 1475-097X
pISSN - 1475-0961
DOI - 10.1111/j.1475-097x.2004.00558.x
Subject(s) - endocrinology , medicine , diabetes mellitus , sensory nerve , c peptide , insulin , proinsulin , glomerular hyperfiltration , stimulation , sensory system , diabetic nephropathy , biology , neuroscience
Summary 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 diabetic rats. In patients with type 1 diabetes, beneficial effects have been demonstrated on sensory nerve conduction velocity, vibration perception and autonomic nerve function. C‐peptide also augments blood flow in several tissues in type 1 diabetes via its stimulation of endothelial NO release, emphasizing a role for C‐peptide in maintaining vascular homeostasis. Continued research is needed to establish whether, among the hormones from the islets of Langerhans, C‐peptide is the ugly duckling that – nearly 40 years after its discovery – may prove to be an endogenous peptide hormone of importance in the treatment of diabetic long‐term complications.