Molecular and cellular effects of C-peptide--new perspectives on an old peptide.
New results present C-peptide as a biologically active peptide hormone in its own right. Although C-peptide is formed from proinsulin and cosecreted with insulin, it is a separate entity with biochemical and physiological characteristics that differ from those of insulin. There is direct evidence of stereospecific binding of C-peptide to a cell surface receptor, which is different from those for insulin and other related hormones. The C-peptide binding site is most likely a G-protein-coupled receptor. The association constant for C-peptide binding is approximately 3 x 10(9) M(-1). Saturation of the binding occurs already at a concentration of about 1 nM, which explains why C-peptide effects are not observed in healthy subjects. Binding of C-peptide results in activation of Ca2+ and MAPK-dependent pathways and stimulation of Na+,K(+)-ATPase and eNOS activities. The latter 2 enzymes are both deficient in several tissues in type 1 diabetes. There is some evidence that C-peptide, and insulin may interact synergistically on the insulin signaling pathway. Clinical evidence suggests that replacement of C-peptide, together with regular insulin therapy, may be beneficial in patients with type 1 diabetes and serve to retard or prevent the development of long-term complications.
Wahren
John
J
Department of Surgical Sciences, Section of Clinical Physiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. john.wahren@creativepeptides.se
Shafqat
Jawed
J
Johansson
Jan
J
Chibalin
Alexander
A
Ekberg
Karin
K
Jörnvall
Hans
H
D000595:Amino Acid Sequence; D000818:Animals; D002096:C-Peptide / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D002096:C-Peptide; D007328:Insulin; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D020928:Mitogen-Activated Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium