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Dipeptidyl peptidase-4 inhibitor: Wikis

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GLP-1 and DPP-4 inhibitors

Inhibitors of Dipeptidyl peptidase 4 , also DPP-4 inhibitors, are a class of oral hypoglycemics that block DPP-4. They can be used to treat diabetes mellitus type 2.

The first agent of the class - sitagliptin - was approved by the FDA in 2006.[1] Sitagliptin entered the Australian drug market in late 2007 for the treatment of difficult-to-control diabetes mellitus type 2.

Their mechanism of action is thought to result from increased Incretin levels (GLP-1 and GIP),[2][3][4] which inhibit glucagon release, the effect of which, in turn, decreases blood glucose, but, more significant, increases insulin secretion and decreases gastric emptying.

Contents

Examples

Drugs belonging to this class are :

Berberine, the common herbal dietery supplement, too inhibits dipeptidyl peptidase-4, which at least partly explains its anti-hyperglycemic activities.[7]

Possible cancer risk

Although extensive long-term, pre-clinical studies of the major DPP-4 inhibitors has failed to show any evidence of potential to cause tumors in laboratory animals, there was one in-vitro (i.e., test tube) study that has raised some questions.[8]

In theory, DPP-4 inhibitors may allow some cancers to progress, since DPP-4 appears to work as a suppressor in the development of cancer and tumours.[9][8][10]

See also

References

  1. ^ U.S. Food and Drug Administration (October 17, 2006). "FDA Approves New Treatment for Diabetes". Press release. http://www.fda.gov/bbs/topics/NEWS/2006/NEW01492.html. Retrieved 2006-10-17.  
  2. ^ McIntosh CH, Demuth HU, Pospisilik JA, Pederson R (June 2005). "Dipeptidyl peptidase IV inhibitors: how do they work as new antidiabetic agents?". Regul. Pept. 128 (2): 159–65. doi:10.1016/j.regpep.2004.06.001. PMID 15780435.  
  3. ^ Behme MT, Dupré J, McDonald TJ (April 2003). "Glucagon-like peptide 1 improved glycemic control in type 1 diabetes". BMC Endocr Disord 3 (1): 3. doi:10.1186/1472-6823-3-3. PMID 12697069.  
  4. ^ Dupre J, Behme MT, Hramiak IM, McFarlane P, Williamson MP, Zabel P, McDonald TJ (June 1995). "Glucagon-like peptide I reduces postprandial glycemic excursions in IDDM". Diabetes 44 (6): 626–30. PMID 7789625.  
  5. ^ Banting and Best Diabetes Centre at UT sitagliptin
  6. ^ Banting and Best Diabetes Centre at UT vildagliptin
  7. ^ Al-Masri IM, Mohammad MK, Tahaa MO.(July 2009)"Inhibition of dipeptidyl peptidase IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of berberine". J Enzyme Inhib Med Chem.PubMed
  8. ^ a b Masur K, Schwartz F, Entschladen F, Niggemann B, Zaenker KS (December 2006). "DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells". Regul. Pept. 137 (3): 147–55. doi:10.1016/j.regpep.2006.07.003. PMID 16908079.  
  9. ^ Pro B, Dang NH (October 2004). "CD26/dipeptidyl peptidase IV and its role in cancer". Histol. Histopathol. 19 (4): 1345–51. PMID 15375776. http://www.hh.um.es/Abstracts/Vol_19/19_4/19_4_1345.htm.  
  10. ^ Wesley UV, McGroarty M, Homoyouni A (February 2005). "Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway". Cancer Res. 65 (4): 1325–34. doi:10.1158/0008-5472.CAN-04-1852. PMID 15735018.  

Further reading

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