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C-peptide
C-peptide
General
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Except where noted otherwise, data are given for
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Infobox disclaimer and references


C-peptide is a peptide that 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 be confused with c-reactive protein or Protein C. The first documented use of the C-peptide test was in 1972.

FunctionEdit

Cellular effects of C-peptide: C-peptide binds to a receptor at the cell surface and activates signal transduction pathways that result in stimulation of Na+,K+ATPase and endothelial nitric oxide synthase (eNOS), both of which are enzymes with reduced activities in type I diabetes.

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,[1] such as diabetic neuropathy[2] and other diabetes-induced ailments. In the kidneys, C-peptide prevents diabetic nephropathy,[3][4] and in the heart blood flow is improved in diabetic patients.[5]

In 1997, insulin manufacturer Eli Lilly and Company jointly funded research into C-Peptide as a possible therapeutic. In the research undertaken at Washington University School of Medicine in St. Louis, researchers 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.[6][7] However, the company never pursued commercialization of the product. But in a 2007 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.

UsesEdit

  • Newly diagnosed diabetes patients often get their C-peptide levels measured as a means of distinguishing type 1 diabetes and type 2 diabetes. C-peptide levels are measured instead of insulin levels 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 in the plasma, but this varies with the nutritional state. The pancreas of patients with type 1 diabetes is unable to produce insulin and therefore they will usually have a decreased level of C-peptide, whereas C-peptide levels in type 2 patients are 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 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 that include pancreatic, parathyroid, and pituitary adenomas, higher levels of C-peptide together with the presence of a gastrinoma suggest that organs besides the stomach may harbor neoplasms.
  • Can be used for identifying factitious disorder: Hypoglycemia with low C-peptide level may indicate abuse of insulin.
  • C-peptide levels are checked in women with Polycystic Ovarian Syndrome (PCOS) to determine degree of insulin resistance.

Both excess body weight and a high plasma concentration of C-peptide predispose men with a subsequent diagnosis of prostate cancer to an increased likelihood of dying of the disease, according to the results of a long-term survival analysis reported in the October 6, 2008 Online First issue of Lancet Oncology.

TherapeuticsEdit

C-peptide has been administered experimentally to improve neuropathy and other symptoms of diabetes.[8] [1] [9] [10] [11] [12] [13] [14] [15].

A company based in La Jolla, California called [[Cebix Incorporated has secured manufacturing and other patents in a number of countries for C-peptide, and aims to commercialize it as a therapeutic for diabetic neuropathy, retinopathy and nephropathy. The peptide is currently being formulated into a once-weekly subcutaneous use and a pivotal phase 2b study in diabetic neuropathy will be initiated early 2011.

External linksEdit

ReferencesEdit

  1. 1.0 1.1 Marques RG, Fontaine MJ, Rogers J (2004). C-peptide: much more than a byproduct of insulin biosynthesis. Pancreas 29 (3): 231–8.
  2. C-Peptide Reverses Nociceptive Neuropathy in Type 1 Diabetes - Kamiya et al. 55 (12): 3581 - Diabetes
  3. Beneficial effects of C-peptide on incipient nephr...[Diabet Med. 2000] - PubMed Result
  4. C-peptide prevents glomerular hypertrophy and mesangial matrix expansion in diabetic rats - Samnegård et al. 20 (3): 532 - Nephrology Dialysis Transplantation
  5. C-Peptide Exerts Beneficial Effects on Myocardial Blood Flow and Function in Patients With Type 1 Diabetes - Hansen et al. 51 (10): 3077 - Diabetes
  6. 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.
  7. Protein Reverses Vascular and Nerve Damage in Diabetic Rats, Washington University School of Medicine Press Release, July 24, 1997.
  8. Johansson BL, Borg K, Fernqvist-Forbes E, Kernell A, Odergren T, Wahren J (2000). Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with Type 1 diabetes mellitus. Diabet. Med. 17 (3): 181–9.
  9. Wahren J, Ekberg K, Samnegård B, Johansson BL (2001). C-peptide: a new potential in the treatment of diabetic nephropathy. Curr. Diab. Rep. 1 (3): 261–6.
  10. Wahren J (2004). C-peptide: new findings and therapeutic implications in diabetes. Clin Physiol Funct Imaging 24 (4): 180–9.
  11. Kamiya H, Zhang W, Sima AA (2004). C-peptide prevents nociceptive sensory neuropathy in type 1 diabetes. Ann. Neurol. 56 (6): 827–35.
  12. Ziegler D (2004). Polyneuropathy in the diabetic patient--update on pathogenesis and management. Nephrol. Dial. Transplant. 19 (9): 2170–5.
  13. Wahren J, Ekberg K, Jörnvall H (2007). C-peptide is a bioactive peptide. Diabetologia 50 (3): 503–9.
  14. Wahren, J (February 2007). C-peptide and Neuropathy in Type 1 Diabetes. Immunology, Endocrine & Metabolic Agents - Medicinal Chemistry 7: 69–77.
  15. Dan Ziegler. [http://www.medforum.nl/idm/IDM1332001LA.pdf New drugs to prevent or treat diabetic polyneuropathy]. (pdf) URL accessed on 2008-01-07.

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