User:Andrew Nguyen/Sandbox 1: Difference between revisions
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== Structural Highlights == | == Structural Highlights == | ||
Januvia is an aromatic compound with a terminal polar <scene name='74/745984/Tfp/3'>trifluorophenyl group</scene> and a <scene name='74/745984/Tfm/1'>trifluoromethyl group</scene>. The enzyme DPP-4 consists of a <scene name='Sitagliptin/Hdryo/1'>hydrophobic serine (S1) pocket</scene> and other <scene name='Sitagliptin/Hbond/2'>hydrogen bonding residues</scene>. Residues of importance for binding purposes between the enzyme DPP-4 and Januvia include the <scene name='Sitagliptin/Bound/1'>catalytic triad</scene> (Ser630, His740, and Asp708) and two glutamates (Glu205 and Glu206).<ref name= "PDB">Ghosh, S. & Goodsell, D. Dipeptidyl Peptidase 4: Protein Data Bank (PDB). (2016) | Januvia is an aromatic compound with a terminal polar <scene name='74/745984/Tfp/3'>trifluorophenyl group</scene> and a <scene name='74/745984/Tfm/1'>trifluoromethyl group</scene>. The enzyme DPP-4 consists of a <scene name='Sitagliptin/Hdryo/1'>hydrophobic serine (S1) pocket</scene> and other <scene name='Sitagliptin/Hbond/2'>hydrogen bonding residues</scene>. Residues of importance for binding purposes between the enzyme DPP-4 and Januvia include the <scene name='Sitagliptin/Bound/1'>catalytic triad</scene> (Ser630, His740, and Asp708) and two glutamates (Glu205 and Glu206).<ref name= "PDB">Ghosh, S. & Goodsell, D. Dipeptidyl Peptidase 4: Protein Data Bank (PDB). (2016) | ||
[http://dx.doi | [http://dx.doi.org/10.2210/rcsb_pdb/mom_2016_10 doi:10.2210/rcsb_pdb/mom_2016_10]</ref> | ||
== Function == | == Function == | ||
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== Agonistic Effects == | == Agonistic Effects == | ||
The incretin hormones GLP-1 and GIP are released by the intestine and signal the synthesis and release of insulin from pancreatic beta-cells.<ref name="NIH" /> Type 2 diabetes has been correlated to a progressive decline in beta-cell numbers and function, leading to insulin deficiency. DPP-4 inhibitors, such as Januvia, increase levels of active GLP-1 after a meal and reduces the glycemic parameters HbA1c, and fasting and postprandial glucose concentrations. Higher levels of GLP-1 have been shown to promote beta-cell proliferation and reduce the chance of beta-cell death.<ref name= "WILEY">doi:10.1111/j.1742-1241.2006.01178.x</ref> The preservation, neogenesis, or restoration of beta-cell function is vital in altering the progression of defective insulin secretions. Current research suggests Januvia and other DPP-4 inhibitors not only sustain glycaemic control, but are also potentially involved in tissue repair, anti-inflammatory mechanisms, and the enhancement of immunotherapy in cancer treatment.<ref name= "OMEGA">Sarkar, M., et al. Double Edge Effect of DPP4 Inhibitor Sitagliptin, A Type-2 Anti-Diabetic Drug, on Inflammation, Injury and Cancer. (2016) J Stem Cell Regen Biol 2(3): 1- 7. [http://dx.doi | The incretin hormones GLP-1 and GIP are released by the intestine and signal the synthesis and release of insulin from pancreatic beta-cells.<ref name="NIH" /> Type 2 diabetes has been correlated to a progressive decline in beta-cell numbers and function, leading to insulin deficiency. DPP-4 inhibitors, such as Januvia, increase levels of active GLP-1 after a meal and reduces the glycemic parameters HbA1c, and fasting and postprandial glucose concentrations. Higher levels of GLP-1 have been shown to promote beta-cell proliferation and reduce the chance of beta-cell death.<ref name= "WILEY">doi:10.1111/j.1742-1241.2006.01178.x</ref> The preservation, neogenesis, or restoration of beta-cell function is vital in altering the progression of defective insulin secretions. Current research suggests Januvia and other DPP-4 inhibitors not only sustain glycaemic control, but are also potentially involved in tissue repair, anti-inflammatory mechanisms, and the enhancement of immunotherapy in cancer treatment.<ref name= "OMEGA">Sarkar, M., et al. Double Edge Effect of DPP4 Inhibitor Sitagliptin, A Type-2 Anti-Diabetic Drug, on Inflammation, Injury and Cancer. (2016) J Stem Cell Regen Biol 2(3): 1- 7. [http://dx.doi.org/10.15436/2471-0598.16.017 doi:10.15436/2471-0598.16.017]</ref> | ||
== Prolonged Treatment == | == Prolonged Treatment == | ||