Intracellular signalling by C-peptide.
C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na(+)/K(+) ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes.
Hills
Claire E
CE
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester School of Medicine, P.O. Box 138, Leicester LE1 7RH, England, UK.
Brunskill
Nigel J
NJ
D000818:Animals; D002096:C-Peptide / Q000494:pharmacology* / Q000502:physiology / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D006801:Humans; D007328:Insulin / Q000502:physiology; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D002096:C-Peptide; D007328:Insulin; D052250:Nitric Oxide Synthase Type III; D020929:Mitogen-Activated Protein Kinase Kinases; D000254:Sodium-Potassium-Exchanging ATPase