C-peptide
From Wikipedia, the free encyclopedia
| C-peptide[1] | |
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| Identifiers | |
| CAS number | [] |
| PubChem | |
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| Properties | |
| Molecular formula | C112H179N35O46 |
| Molar mass | 2751.82656 |
| Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox references |
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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.
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[edit] Function
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 activitities 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,[2] such as diabetic neuropathy[3] and other diabetes-induced ailments. In the kidneys, C-peptide prevents diabetic nephropathy,[4][5] and in the heart blood flow is improved in diabetic patients.[6]
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. The historical reason for this is that some patients suffered allergic reactions to what was believed to be bovine and porcine C-peptide when pharmaceutical insulin was still manufactured from cow or pig insulin and the methods for purification were less advanced.
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.[7][8] 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.
[edit] Uses
- 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 which 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.
[edit] Therapeutics
C-peptide has been administered experimentally to improve neuropathy and other symptoms of diabetes.[9] [10] [11] [12] [13] [2] [14] [15] [16].
A company based in Stockholm, Sweden called 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. However since C-Peptide was discovered in 1967, patenting the peptide itself is not possible, only the processes to create it. This makes it very difficult to obtain research dollars from pharmaceutical companies to conduct research. Creative Pepides solution is to patent processes to create C-Peptide, thus making the product more profitable to invest in for pharmaceutical companies.
After delays due to lack of funding, Creative Peptides has now obtained funding based on a process that will make it possible to inject C-peptide once a week instead of daily. Stage 3 Clinical Trials are set for late 2009.
[edit] References
- ^ C-Peptide - Compound Summary, PubChem.
- ^ a b Marques RG, Fontaine MJ, Rogers J (2004). "C-peptide: much more than a byproduct of insulin biosynthesis". Pancreas 29 (3): 231–8. PMID 15367890.
- ^ C-Peptide Reverses Nociceptive Neuropathy in Type 1 Diabetes - Kamiya et al. 55 (12): 3581 - Diabetes
- ^ Beneficial effects of C-peptide on incipient nephr...[Diabet Med. 2000] - PubMed Result
- ^ C-peptide prevents glomerular hypertrophy and mesangial matrix expansion in diabetic rats - Samnegård et al. 20 (3): 532 - Nephrology Dialysis Transplantation
- ^ C-Peptide Exerts Beneficial Effects on Myocardial Blood Flow and Function in Patients With Type 1 Diabetes - Hansen et al. 51 (10): 3077 - Diabetes
- ^ 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.
- ^ Protein Reverses Vascular and Nerve Damage in Diabetic Rats, Washington University School of Medicine Press Release, July 24, 1997.
- ^ 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. doi:. PMID 10784221. "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.".
- ^ 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. doi:. PMID 12643208. "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.".
- ^ Wahren J (2004). "C-peptide: new findings and therapeutic implications in diabetes". Clin Physiol Funct Imaging 24 (4): 180–9. doi:. PMID 15233831. "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.".
- ^ Kamiya H, Zhang W, Sima AA (2004). "C-peptide prevents nociceptive sensory neuropathy in type 1 diabetes". Ann. Neurol. 56 (6): 827–35. doi:. PMID 15497155. "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.".
- ^ Ziegler D (2004). "Polyneuropathy in the diabetic patient--update on pathogenesis and management". Nephrol. Dial. Transplant. 19 (9): 2170–5. doi:. PMID 15252164. http://ndt.oxfordjournals.org/cgi/reprint/19/9/2170. Retrieved on 2008-01-07.
- ^ Wahren J, Ekberg K, Jörnvall H (2007). "C-peptide is a bioactive peptide". Diabetologia 50 (3): 503–9. doi:. PMID 17235526.
- ^ Wahren, J (February 2007). "C-peptide and Neuropathy in Type 1 Diabetes". Immunology, Endocrine & Metabolic Agents - Medicinal Chemistry 7 (1): 69–77. http://www.ingentaconnect.com/content/ben/iemamc/2007/00000007/00000001/art00008. Retrieved on 2008-01-07. "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.".
- ^ Dan Ziegler. "[http://www.medforum.nl/idm/IDM1332001LA.pdf New drugs to prevent or treat diabetic polyneuropathy]" (pdf). http://www.medforum.nl/idm/IDM1332001LA.pdf. Retrieved on 2008-01-07.
