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| − | <p>Canagliflozin, also known as Invokana, is a drug developed by Mitsubishi Tanabe Pharma as an insulin independent treatment for type II diabetes. The drug targets the SGLT2 protein in the proximal tubule of the kidney. SGLT2 is responsible for the reabsorption of 90% of glucose in the kidney. By directly inhibiting the actions of SGLT2, Invokana is able to reduce the amount of glucose reabsorbed into the body and excrete the glucose via urination. The activity of the drug reached its optimal peak one to two hours after intake. According to test trials done by the developer, side effects such as urinary tract infection and hypoglycemia were not detected. Although consuming the drug did increase the risk of dehydration<sup>12</sup>.</p>
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| − | <p>Our team looked for a biological drug capable of doing the same job as Invokana. QSP is a tripeptide produced by humans naturally that has a similar function to Invokana. The human RSC1A1 gene codes for the tripeptide. Although QSP has the same effects as Invokana, its working mechanism is significantly different. Invokana works by directly inhibiting the STLG2 membrane proteins and thereby inhibit the reabsorption of glucose. However, QSP works as a post-transcriptional inhibitor of STLG2 at the trans-Golgi network (TGN). The tripeptides reduces the expression of STLG2 by 40%-50% at the plasma membrane<sup>13</sup>. </p>
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| − | <p>The model we used for tripeptide production is the sausage-protease model. Since the tripeptides are coded for by only nine base pairs, it is hard for transcriptional factors to transcribe it. In addition, the start codon in the beginning of the sequence disrupts the function of the protein. Thus we came up with the sausage model of tripeptides. The sequence for the tripeptides will be repeated several times so when the gene is transcribed there is three copies of tripeptides. At the end of the tripeptide link there is a HLY secretion tag. We also engineered another cell that contains a protease attached to the outer membrane of E. coli via an ompA membrane protein. The tripeptides will be secreted out of the cell into the extracellular environment where it will meet up with the protease to receive its final modifications. The protease will cut the sausage tripeptides into individual units before it enters the bloodstream.</p>
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| − | <h5 id=cow>Citations</h5>
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| − | <li>National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States (2014): n. pag. Centers for Disease Control and Prevention. U.S. Department of Health and Human Services, 2014. Web. 11 Sept. 2015.</li>
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| − | <li>"Number (in Millions) of Civilian, Noninstitutionalized Persons with Diagnosed Diabetes, United States, 1980–2011." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 28 Mar. 2013. Web. 10 Sept. 2015.</li>
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| − | <li>"Leading Causes of Death." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 21 Aug. 2015. Web. 8 Sept. 2015.</li>
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| − | <li>"Up to 40 Percent of Annual Deaths from Each of Five Leading US Causes Are Preventable." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 01 May 2014. Web. 10 Sept. 2015.</li>
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| − | <li>Lebovitz, Harold. "Type 2 Diabetes: An Overview." Clinical Chemistry 45.8 (1999): 1339-345. Type 2 Diabetes: An Overview. Web. 10 Sept. 2015.</li>
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| − | <li>Wilcox, Gisela. "Insulin and Insulin Resistance." Clinical Biochemist Review26.2 (2005): 19-39. Web. 11 Sept. 2015.</li>
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| − | <li>"Insulin Resistance." National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 7 Sept. 2015.</li>
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| − | <li>"Thiazolidinediones." U.S National Library of Medicine. U.S. National Library of Medicine, n.d. Web. 11 Sept. 2015.</li>
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| − | <li>"Hyperglycemia." National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 11 Sept. 2015.</li>
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| − | <li>Yoshida, T., L. Qin, L. A. Egger, and M. Inouye. "Transcription Regulation of OmpF and OmpC by a Single Transcription Factor, OmpR." Journal of Biological Chemistry (2006): 17114-7123. Print.</li>
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| − | <li>Fatimathas, Lux. "Structural Changes in Bacterial Osmosensing." « Mechanobiology Institute, Singapore. Web. 11 Sept. 2015.</li>
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| − | <li>Sarnoski-Brocavich, Sheila, and Olga Hilas. "Canagliflozin (Invokana), a Novel Oral Agent For Type-2 Diabetes."Pharmacy and Therapeutics 38.11 (2013): 656-66. Print.</li>
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| − | <li>"Tripeptides of RS1 (RSC1A1) Inhibit a Monosaccharide-dependent Exocytotic Pathway of Na -D-Glucose Cotransporter SGLT1 with High Affinity." The Journal of Biological Chemistry 282.39 (2007). Print.</li>
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