C-peptide

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Reference= [ [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=16132309 C-Peptide - Compound Summary] , PubChem.]
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MeSHName=C-Peptide
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Formula=C₁₁₂H₁₇₉N₃₅O₄₆
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C-peptide is a peptide which is made when proinsulin is split into insulin and C-peptide. They split before proinsulin is released from endocytic vesicles within the pancreas -- one C-peptide for each insulin molecule.

C-peptide is the abbreviation for "connecting peptide", although its name was probably also inspired by the fact that insulin is also composed of an "A" chain and a "B" chain. C-peptide was discovered in 1967. It should not to be confused with c-reactive protein or Protein C. The first documented use of the C-peptide test was in 1972.

Function

C-peptide functions in repair of the muscular layer of the arteries.

C-peptide also exerts beneficial therapeutic effects on many complications associated with diabetes mellitus, such as diabetic neuropathy [ [http://diabetes.diabetesjournals.org/cgi/content/abstract/55/12/3581 C-Peptide Reverses Nociceptive Neuropathy in Type 1 Diabetes - Kamiya et al. 55 (12): 3581 - Diabetes ] ] and other diabetes-induced ailments. In the kidneys, C-peptide prevents diabetic nephropathy, [ [http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=10784221&dopt=AbstractPlus Beneficial effects of C-peptide on incipient nephr... [Diabet Med. 2000 - PubMed Result ] ] [ [http://ndt.oxfordjournals.org/cgi/content/abstract/20/3/532 C-peptide prevents glomerular hypertrophy and mesangial matrix expansion in diabetic rats - Samnegård et al. 20 (3): 532 - Nephrology Dialysis Transplantation ] ] and in the heart blood flow is improved in diabetic patients. [ [http://diabetes.diabetesjournals.org/cgi/content/abstract/51/10/3077 C-Peptide Exerts Beneficial Effects on Myocardial Blood Flow and Function in Patients With Type 1 Diabetes - Hansen et al. 51 (10): 3077 - Diabetes ] ]

In spite of these physiological functions, C-peptide is not present in pharmaceutical preparations of insulin sold by drug companies that are in wide-scale clinical usage today, a practice seen as unethical in light of more research suggesting the peptide's utility.

Ironically, back in 1997, insulin manufacturer Eli Lilly and Company jointly funded research into C-Peptide as a possible therapeutic. In the research undertaken by researchers at Washington University School of Medicine in St. Louis, they determined that C-Peptide may effectively prevent and even reverse cardiovascular disease and nerve damage in people with diabetes, although their studies were only on rodent models of the disease. [ [http://www.sciencemag.org/cgi/content/short/277/5325/563 Y. Ido, A. Vindigni, K. Chang, L. Stramm, R. Chance, W. F. Heath, R. D. DiMarchi, E. Di Cera, J. R. Williamson, "Prevention of Vascular and Neural Dysfunction in Diabetic Rats by C-Peptide", Science 25 July 1997: Vol. 277. no. 5325, pp. 563-566; DOI: 10.1126/science.277.5325.56.] ] [ [http://aladdin.wustl.edu/medadmin/panews.nsf/0/60A083A93302B4FA86256B20006CA6B9 Protein Reverses Vascular and Nerve Damage in Diabetic Rats, Washington University School of Medicine Press Release, July 24, 1997.] ] However, the company never pursued commercialization of the product. But in 2007 a letter to the "Indianapolis Star", company executive John C. Lechleiter did indicate that the company was pursuing development of drugs to treat diabetes-induced complications.

Uses

* Newly diagnosed diabetes patients often get their C-peptide levels measured, to find if they have type 1 diabetes or type 2 diabetes. The reason that the C-peptide levels are measured instead of the insulin levels themselves is because insulin concentration in the portal vein ranges from two to ten times higher than in the peripheral circulation. The liver extracts about half the insulin reaching it (the plasma), but this varies with the nutritional state. The pancreas of patients with type 1 diabetes is unable to produce insulin and they will therefore usually have a decreased level of C-peptide, while C-peptide levels in type 2 patients is normal or higher than normal. Measuring C-peptide in patients injecting insulin can help to determine how much of their own natural insulin these patients are still producing.C-peptide is also easily detected because antibodies that are sensitive to it are readily available, whereas antibodies to insulin are much more difficult to obtain.

* C-peptide is also used for determining the possibility of gastrinomas associated with Multiple Endocrine Neoplasm syndromes (MEN 1). Since a significant amount of gastrinomas also include MEN which include pancreatic, parathyroid, and pituitary adenomas, higher levels of c-protein in addition to a gastrinoma may suggest other organs than just the stomach may include neoplasms.
* Can be used for identifying malingering: hypoglycemia with low C-peptide level may indicate abuse of insulin.

C-peptide levels are also checked to determine how insulin resistant women with Polycystic Ovarian Syndrome may be.

Therapeutics

C-peptide has been administered experimentally to improve neuropathy and other symptoms of diabetes.cite journal |author=Johansson BL, Borg K, Fernqvist-Forbes E, Kernell A, Odergren T, Wahren J |title=Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with Type 1 diabetes mellitus |journal=Diabet. Med. |volume=17 |issue=3 |pages=181–9 |year=2000 |pmid=10784221 |doi=10.1046/j.1464-5491.2000.00274.x
quote=Respiratory heart rate variability increased by 21 +/- 9% (P < 0.05) during treatment with C-peptide [...] C-peptide ameliorates autonomic and sensory nerve dysfunction in patients with Type 1 diabetes mellitus.|accessdate=2008-01-07] cite journal |author=Wahren J, Ekberg K, Samnegård B, Johansson BL |title=C-peptide: a new potential in the treatment of diabetic nephropathy |journal=Curr. Diab. Rep. |volume=1 |issue=3 |pages=261–6 |year=2001 |pmid=12643208 |doi=10.1007/s11892-001-0044-4
quote=Administration of C-peptide to physiologic concentrations in patients with type 1 diabetes and incipient nephropathy for periods of 3 hours to 3 months is accompanied by reduced glomerular hyperfiltration and filtration fraction, and diminished urinary albumin excretion. C-peptide replacement together with insulin therapy may be beneficial in type 1 diabetes patients with nephropathy.|accessdate=2008-01-07] cite journal |author=Wahren J |title=C-peptide: new findings and therapeutic implications in diabetes |journal=Clin Physiol Funct Imaging |volume=24 |issue=4 |pages=180–9 |year=2004 |pmid=15233831 |doi=10.1111/j.1475-097X.2004.00558.x
quote=In patients with type 1 diabetes, beneficial effects have been demonstrated on sensory nerve conduction velocity, vibration perception and autonomic nerve function. C-peptide also augments blood flow in several tissues in type 1 diabetes via its stimulation of endothelial NO release, emphasizing a role for C-peptide in maintaining vascular homeostasis.
accessdate=2008-01-07] cite journal |author=Kamiya H, Zhang W, Sima AA |title=C-peptide prevents nociceptive sensory neuropathy in type 1 diabetes |journal=Ann. Neurol. |volume=56 |issue=6 |pages=827–35
quote=we conclude that replacement of insulinomimetic C-peptide prevents abnormalities of neurotrophins, their receptors, and nociceptive neuropeptides in type 1 BB/Wor-rats, resulting in the prevention of C-fiber pathology and nociceptive sensory nerve dysfunction. The data indicate that perturbed insulin/C-peptide action plays an important pathogenetic role in nociceptive sensory neuropathy and that C-peptide replacement may be of benefit in treating painful diabetic neuropathy in insulin-deficient diabetic conditions.
year=2004 |pmid=15497155 |doi=10.1002/ana.20295 |accessdate=2008-01-07] cite journal |author=Ziegler D |title=Polyneuropathy in the diabetic patient--update on pathogenesis and management |journal=Nephrol. Dial. Transplant. |volume=19 |issue=9 |pages=2170–5 |year=2004 |url=http://ndt.oxfordjournals.org/cgi/reprint/19/9/2170|pmid=15252164 |doi=10.1093/ndt/gfh398 |accessdate=2008-01-07] cite journal |author=Marques RG, Fontaine MJ, Rogers J |title=C-peptide: much more than a byproduct of insulin biosynthesis |journal=Pancreas |volume=29 |issue=3 |pages=231–8 |year=2004 |pmid=15367890 |doi= |accessdate=2008-01-07] cite journal |author=Wahren J, Ekberg K, Jörnvall H |title=C-peptide is a bioactive peptide |journal=Diabetologia |volume=50 |issue=3 |pages=503–9 |year=2007 |pmid=17235526 |doi=10.1007/s00125-006-0559-y |accessdate=2008-01-07] cite journal|url=http://www.ingentaconnect.com/content/ben/iemamc/2007/00000007/00000001/art00008 |title=C-peptide and Neuropathy in Type 1 Diabetes|author=Wahren, J
quote=C-peptide corrects diabetes-induced reductions in endoneurial blood flow and in Na+,K+-ATPase activity. In vitro studies demonstrate that C-peptide binds specifically to cell membranes, activating a G-protein coupled receptor as well as Ca2+-, PKC- and MAPK-dependent signaling pathways, resulting in stimulation of Na+,K+-ATPase and endothelial nitric oxide synthase (eNOS). In addition, C-peptide activates transcription factors resulting in augmented eNOS mRNA and protein content of endothelial cells and modulation of neurotrophic factors as well as apoptotic phenomena in neuroblastoma cells. Combined, the results demonstrate that C-peptide is a bioactive peptide, possibly of importance in the treatment of neuropathy in type 1 diabetes.|journal=Immunology, Endocrine & Metabolic Agents - Medicinal Chemistry |volume =7|number =1|month= February | year= 2007 |pages= 69–77
accessdate=2008-01-07 |format= |work=] cite web |url=http://www.medforum.nl/idm/IDM1332001LA.pdf |title=New drugs to prevent or treat diabeticpolyneuropathy|author=Dan Ziegler |accessdate=2008-01-07 |format= pdf|work=] .

A company based in Stockholm, Sweden called [http://www.creativepeptides.se/company.html Creative Peptides] has secured manufacturing and other patents in a number of countries for C-peptide, and aims to commercialize it as a therapeutic. It is now undergoing human clinical trials.

References