Proinsulin C-peptide is the sequence of C peptide as it exists within proinsulin, the precursor to insulin which consists of insulin A chain, insulin B chain and C peptide (connecting peptide). In proinsulin, C peptide provides a means to ensure correct folding and assembly of the A and B chains. It is eventually cleaved away by proteases PC2, PC1/3 and CPE, at the flanking Arg-Arg and Lys-Arg basic residues (Arg-Arg-C peptide-Lys-Arg). Although C peptide is not present in mature insulin, it is stored in secretory granules, and eventually released into the bloodstream together with insulin in nearly equimolar amounts. Whereas insulin is metabolized quickly from circulation, C-peptide exhibits a slow turnover rate (>30 minutes). The measurement of the C-peptide is an important test for the β-cell function. In the red blood cells of type 2 diabetic patients, Na+,K+, ATPase activity is strongly related to blood C-peptide levels. C-peptide signal transduction in human renal tubular cells involves the activation of phospholipase C and PKC-d and PKC-varepsilon, as well as RhoA, followed by phosphorylation of ERK1/2 and JNK and a parallel activation of Akt. C-peptide shows specific binding to a G-protein-coupled membrane binding site, resulting in Ca2+ influx, activation of mitogen-activated protein kinase signalling pathways and stimulation of Na+, K+ ATPase and endothelial nitric oxide synthase.