Role of C-peptide in human physiology.
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.
Wahren
J
J
Department of Surgical Sciences, Section of Clinical Physiology, Karolinska Hospital, SE-171 76 Stockholm, Sweden. john.wahren@ks.se
Ekberg
K
K
Johansson
J
J
Henriksson
M
M
Pramanik
A
A
Johansson
B L
BL
Rigler
R
R
Jörnvall
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000502:physiology; D008969:Molecular Sequence Data; D009424:Nervous System Physiological Phenomena; D010827:Physiology; D017385:Sequence Homology; D015398:Signal Transduction
D001786:Blood Glucose; D002096:C-Peptide