The Relevance of C-Peptide in Diabetes and its Complications: An Introduction to the Special Issue

It is well accepted that the connecting peptide (C-peptide) of proinsulin is a critical element in the biosynthesis of insulin. It facilitates the proinsulin molecule’s proper folding. Following cleavage of proinsulin, the two resultant peptides are stored in secretory granules in the beta-cells and eventually co-released into the circulation in equal concentrations. The possibility that Cpeptide may possess biological activity on its own was a consideration at the time of its discovery in 1968. However, no detectable influence on glucose metabolism in humans, or on lipolysis of isolated fat cells, could be observed. Consequently, the focus on C-peptide as a bioactive peptide diminished, and instead, interest centered on its usefulness as a marker of insulin secretion. In the early 1990s, direct C-peptide effects were re-evaluated in a new setting. Several studies were undertaken involving administration of the peptide to type 1 diabetes patients, who otherwise lacked C-peptide. This approach gave positive results. It emerged that replacement of physiological concentrations of C-peptide in this patient group resulted in significant improvements of diabetes-induced abnormalities in peripheral nerves and kidney functions. In addition, C-peptide was found to significantly augment the blood flow in skeletal muscle, myocardium, skin, and the kidney. Read more...