C-peptide as a therapeutic tool in diabetic nephropathy.
OBJECTIVE
Insulin is synthesised as a pro-hormone with an interconnecting C-peptide, cleaved during post-translational modification. This review discusses growing evidence which indicates that C-peptide is biologically active, benefiting microvascular complications associated with diabetes.


METHODS
To explore the renoprotective role of C-peptide in diabetic nephropathy (DN), we reviewed the literature using PubMed for English language articles that contained key words related to C-peptide, kidney and DN.


RESULTS
Numerous studies have demonstrated that C-peptide ameliorates a number of the structural and functional renal disturbances associated with uncontrolled hyperglycaemia in human and animal models of type 1 diabetes mellitus that lead to the development and progression of nephropathy, including abrogation of glomerular hyperfiltration, reduced microalbuminuria, decreased mesangial expansion and increased endothelial nitric oxide synthase levels. The in vitro exposure of kidney proximal tubular cells to physiological concentrations of C-peptide activates extracellular signal-regulated kinase, phosphatidylinositol 3-kinase, protein kinase C, elevates intracellular calcium, and stimulates transcription factors NF-kappaB and peroxisome proliferator-activated receptor-gamma.


CONCLUSIONS
Burgeoning studies suggest that C-peptide is more than merely a link between the A and B chains of the proinsulin molecule and represents a future therapeutic tool in reducing complications of DN.
Hills
Claire E
CE
Department of Biological Sciences, University of Warwick, Coventry, UK. C.Hills @ warwick.ac.uk
Brunskill
Nigel J
NJ
Squires
Paul E
PE
D000818:Animals; D002096:C-Peptide / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000628:therapy; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D018450:Disease Progression; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000628:therapy; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D002096:C-Peptide; D016328:NF-kappa B; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase