C-peptide

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C-peptide
Identifiers
CAS number
PubChem 16132309
MeSH C-Peptide
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 disclaimer and references

C-peptide is a peptide which is made when proinsulin is split into insulin and C-peptide. They split when proinsulin is released from the pancreas into the blood in response to a rise in serum glucose - 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.

Contents

[edit] 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 [1] , [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 [6] blood flow is improved in diabetic patients.

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.

[edit] 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.

[edit] Therapeutics

C-peptide has been administered experimentally to improve neuropathy and other symptoms of diabetes.[7] [8] [9] [10] [11] [1] [12] [13] [14] 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.

[edit] References

  1. ^ 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. 
  2. ^ Science/AAAS | Science Magazine: Sign In
  3. ^ C-Peptide Reverses Nociceptive Neuropathy in Type 1 Diabetes - Kamiya et al. 55 (12): 3581 - Diabetes
  4. ^ Beneficial effects of C-peptide on incipient nephr...[Diabet Med. 2000] - PubMed Result
  5. ^ C-peptide prevents glomerular hypertrophy and mesangial matrix expansion in diabetic rats - Samnegård et al. 20 (3): 532 - Nephrology Dialysis Transplantation
  6. ^ C-Peptide Exerts Beneficial Effects on Myocardial Blood Flow and Function in Patients With Type 1 Diabetes - Hansen et al. 51 (10): 3077 - Diabetes
  7. ^ 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:10.1046/j.1464-5491.2000.00274.x. 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.” 
  8. ^ 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:10.1007/s11892-001-0044-4. 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.” 
  9. ^ Wahren J (2004). "C-peptide: new findings and therapeutic implications in diabetes". Clin Physiol Funct Imaging 24 (4): 180–9. doi:10.1111/j.1475-097X.2004.00558.x. 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.” 
  10. ^ Kamiya H, Zhang W, Sima AA (2004). "C-peptide prevents nociceptive sensory neuropathy in type 1 diabetes". Ann. Neurol. 56 (6): 827–35. doi:10.1002/ana.20295. 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.” 
  11. ^ Ziegler D (2004). "Polyneuropathy in the diabetic patient--update on pathogenesis and management". Nephrol. Dial. Transplant. 19 (9): 2170–5. doi:10.1093/ndt/gfh398. PMID 15252164. 
  12. ^ Wahren J, Ekberg K, Jörnvall H (2007). "C-peptide is a bioactive peptide". Diabetologia 50 (3): 503–9. doi:10.1007/s00125-006-0559-y. PMID 17235526. 
  13. ^ Wahren, J (February 2007). "C-peptide and Neuropathy in Type 1 Diabetes". Immunology, Endocrine & Metabolic Agents - Medicinal Chemistry 7: 69-77. “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.” 
  14. ^ Dan Ziegler. [http://www.medforum.nl/idm/IDM1332001LA.pdf New drugs to prevent or treat diabetic polyneuropathy] (pdf). Retrieved on 2008-01-07.
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