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lüll Role of C-peptide in human physiology Wahren J; Ekberg K; Johansson J; Henriksson M; Pramanik A; Johansson BL; Rigler R; Jornvall HAm J Physiol Endocrinol Metab 2000[May]; 278 (5): E759-68The 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.|*Physiology[MESH]|Amino Acid Sequence[MESH]|Animals[MESH]|Blood Glucose/metabolism[MESH]|C-Peptide/*physiology[MESH]|Humans[MESH]|Kidney/physiology[MESH]|Molecular Sequence Data[MESH]|Nervous System Physiological Phenomena[MESH]|Sequence Homology[MESH]|Signal Transduction[MESH] |