User:Andrew Nguyen/Sandbox 1: Difference between revisions

You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

Incretin hormones, Glucagon-like peptide-1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day and levels are increased in response to a meal. When blood glucose concentrations rise above normal levels, GLP-1 and GIP increase insulin secretion and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. In addition, GLP-1 also plays an important role reducing glucagon secretion from pancreatic alpha cells, delaying gastric emptying, and potential induction of satiety. The activity of GLP-1 and GIP is limited by the enzyme Dipeptidyl Peptidase-4 (DPP-4). DPP-4 is an antigenic membrane serine exopeptidase that cleaves proline dipeptides from the N-terminal end of GLP-1 and GIP, rapidly hydrolyzing GLP-1 and GIP to produce inactive products. Januvia (Sitagliptin) is a competitive inhibitor of DPP-4, which prevents the enzymatic hydrolysis of GLP-1 and GIP by DPP-4. Thus, concentrations of the active forms of these incretin hormones are increased, which in turn increase insulin release and decrease glucagon levels by the pancreas in a glucose-dependent manner. Ultimately, these levels of insulin and glucagon result in a decrease in blood glucose levels. In individuals with type 2 diabetes, this lowering or normalization of blood glucose levels can be essential in alleviating major complications and improving overall quality of life. Januvia inhibits DPP-4 by binding to the active site of DPP-4, which consists of a hydrophobic serine (S1) pocket and other hydrogen bonding residues. Januvia situates its trifluorophenyl group within the S1 hydrophobic pocket, forming four hydrogen bond interactions with the residues Glu 205, Glu 206, and Tyr 662, and burying its trifluoro group within a tight pocket formed by residues Ser 209 and Arg 358.  

== Agonistic Effects ==