Sandbox Reserved 918: Difference between revisions

DPP IV is found in diverse tissue types and is involved in various biological functions. The activity of DPP IV has been studied in fields like immunology, endocrinology, and the biology of cancers. <ref name="Gorrell"/> The ability of DPP IV to inactivate [http://en.wikipedia.org/wiki/Incretin incretins] glucagon-like-peptide-1 (GLP-1) and glucose-dependent [http://www.merriam-webster.com/medical/insulinotropic insulinotropic] polypeptide (GIP) have made it a potential drug target for the treatment of [http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 Type II Diabetes].  GLP-1 and GIP promote glucose uptake, decrease the gastric emptying rate and inhibit glucagon secretion. These actions are all desired when it comes to treating Type II diabetes, but the problem is that DPP IV  inactivates GLP-1 and GIP very rapidly (the half-lives of GLP-1 and GIP are less than two minutes). <ref> PMID: 17160910</ref> [http://en.wikipedia.org/wiki/Dipeptidyl_peptidase-4_inhibitor DPP IV inhibitors] prevent DPP IV from inactivating GLP-1 and GIP, which results in improved glucose tolerance, improved pancreatic islet cell function, and a decrease in blood glucose levels. The decrease in blood glucose is associated with increased levels of active circulating GLP-1 and a reduction of glucagon. <ref> PMID: 12892317</ref> <scene name='57/573132/1x70_sitagliptin/3'>Sitagliptin</scene>, also known as Januvia, is a DPP IV inhibitor that's in the incretin mimetic class. It was approved by the FDA for the treatment of type II diabetes in 2006. When given to control subjects, Sitagliptin increases plasma concentrations of GLP-1. Sitagliptin was approved to be used in combination with [http://www.drugs.com/metformin.html metformin] in 2007. <ref> PMID: 17160910</ref> A study done by Williams-Herman et. al showed that initial combination therapy with metformin and sitagliptin resulted in lower blood glucose concentrations at each metformin dose studied than mono therapy of metformin. A majority of the patients in the combination therapy group maintained the desired blood glucose concentration of <7% at the end of the two-year trial period. <ref> PMID: 20415693</ref> This is noteworthy because it's more difficult for people to meet their glycemic goals long term as the disease progresses. Sitagliptin was approved to be administered with sulfonylureas in 2008, which are insulin-secreting agents. Combination therapy of these two drugs requires close monitoring and adjustment of the sulfonylurea dose to prevent hypoglycemia <ref> PMID: 20690781</ref>. Statins, like simvastatin, which help lower cholesterol levels, are also frequently prescribed to patients with Type II diabetes in addition to DPP IV inhibitors like sitagliptin. <ref> PMID: 20690781</ref>