The role of C-peptide in regulation of the insulin signaling system (systematic review)

The C-peptide is a fragment of proinsulin, the cleavage of which forms active insulin. In recent years, new evidence has emerged indicating that C-peptide is involved not only in the processing of insulin in the secretory granules of pancreatic β-cells, but also has an important regulatory effect on the functions of many organs and tissues. C-peptide mediates physiological effects through signaling pathways by binding to a specific receptor on the cell membrane. Intracellular signaling occurs through the G-protein and Ca2+- dependent pathways, which leads to the activation and increased expression of endothelial nitric oxide synthase, Na+/K+-ATPase, and important transcription factors involved in apoptosis, anti-inflammatory and other intracellular defense mechanisms. One of the most important physiological effects of C-peptide is the regulation and modification of insulin signaling mechanisms. The nature of the effect of C-peptide on the insulin signaling system depends on the concentration of insulin. It is assumed that under conditions of low insulin levels, the C-peptide receptor binds to Gi/o-proteins and leads to increased activation of processes induced by insulin. In this case, the C-peptide acts as insulin-mimetic peptide. Under high insulin conditions, the C-peptide receptor binds to Gq/11-proteins and leads to activation of protein kinase C with subsequent weakening of insulin-related signaling cascades. This review presents new facts indicating the participation of C-peptide in the regulation of the insulin signaling system.