Role of C-peptide in human physiology

Abstract

The C-peptide of proinsulin is important for the biosynthesis of insulin but has for a long time been considered to be biologically inert. Data now indicate that C-peptide in the nanomolar concentration range binds specifically to cell surfaces, probably to a G protein-coupled surface receptor, with subsequent activation of Ca(2+)-dependent intracellular signaling pathways. The association rate constant, K(ass), for C-peptide binding to endothelial cells, renal tubular cells, and fibroblasts is approximately 3. 10(9) M(-1). The binding is stereospecific, and no cross-reaction is seen with insulin, proinsulin, insulin growth factors I and II, or neuropeptide Y. C-peptide stimulates Na(+)-K(+)-ATPase and endothelial nitric oxide synthase activities. Data also indicate that C-peptide administration is accompanied by augmented blood flow in skeletal muscle and skin, diminished glomerular hyperfiltration, reduced urinary albumin excretion, and improved nerve function, all in patients with type 1 diabetes who lack C-peptide, but not in healthy subjects. The possibility exists that C-peptide replacement, together with insulin administration, may prevent the development or retard the progression of long-term complications in type 1 diabetes.

Molecular basis for the insulinomimetic effects of C-peptide

“…Firstly, C-peptide effects could result from direct binding to, and activation of, a specific C-peptide receptor. Although the presence of such a receptor has not been unequivocally proven, a putative receptor has been found [2,8]. Investigations suggest that the C-peptide receptor is a surface entity probably coupled to its signal transduction pathway by a G protein.…”

“…Pretreatment of cells with pertussis toxin abolishes specific C-peptide binding [8]. This observation, along with inhibition of several C-peptide effects by pertussis toxin, indicates that C-peptide binds to a G-protein coupled receptor [2,8]. Human C-peptide stimulates glucose transport in human non-diabetic and diabetic skeletal muscle [9,10].…”

Diagnostic performance of the ARCHITECT C-Peptide immunoassay

“…It connects the A and B chains of insulin in the precursor molecule proinsulin, which is stored in secretory granules of the pancreatic b-cell (1-3). C-peptide facilitates the formation of the correct secondary and tertiary structure of the hormone during insulin biosynthesis (3,4). C-peptide and insulin are secreted in equimolar amounts; however, C-peptide does not undergo significant hepatic metabolism.…”

Proinsulin C-peptide activates vagus efferent output in rats

“…Plasma C-peptide levels are often used as a marker of actual insulin secretion, and inversely related to the development of diabetic complications including neuropathy [22,28,29]. For a long time, C-peptide had been considered to be biological inert.…”

“…For a long time, C-peptide had been considered to be biological inert. However, recent studies have shown that C-peptide is an active peptide hormone with potentially important physiological effects against diabetic complications in patients with type 1 diabetes and experimental models [2,4,8,10,11,22,28,29]. For example, short-term infusion of C-peptide improves impaired cardiac autonomic nerve functions, mainly parasympathetic components, in patients with polyneuropathy and type 1 diabetes [10].…”