Molecular Mechanisms of Action and Physiological Effects of the Proinsulin C-Peptide (a Systematic Review)

C-peptide is a proinsulin fragment, which is cleaved during proinsulin maturation and active insulin formation. Evidence obtained in recent years suggests that C-peptide exhibits positive physiological effects on many organs and tissues, including the kidneys, nervous system, heart, vascular endothelium and blood microcirculation. Studies on experimental models of diabetes mellitus in animals, as well as clinical trials in diabetic patients have shown that C-peptide exhibits important regulatory effects at early stages of functional and structural impairments caused by this disease. C-peptide realizes its effects through its binding to a specific receptor on the cell membrane and activation of downstream signaling pathways. Intracellular signaling involves G-proteins and Ca2+-dependent pathways; this leads to 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. This review summarizes existing information about C-peptide as a bioactive endogenous peptide possessing its own biological activity and therapeutic potential.