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| 1 | Pharmacological inhibition of diacylglycerol acyltransferase-1 and insights into postprandial gut peptide secretion显示文摘AIM To examine the role that enzyme Acyl-CoA:diacylglycerol acyltransferase-1(DGAT1) plays in postprandial gut peptide secretion and signaling.METHODS The standard experimental paradigm utilized to evaluate the incretin response was a lipid challenge.Following a lipid challenge,plasma was collected via cardiac puncture at each time point from a cohort of 5-8 mice per group from baseline at time zero to 10 h.Incretin hormones [glucagon like peptide-1(GLP-1),peptide tyrosine-tyrosine(PYY) and glucose dependent insulinotropic polypeptide(GIP)] were then quantitated.The impact of pharmacological inhibition of DGAT1 on the incretin effect was evaluated in WT mice.Additionally,a comparison of loss of DGAT1 function either by genetic ablation or pharmacological inhibition.To further elucidate the pathways and mechanisms involved in the incretin response to DGAT1 inhibition,other interventions [inhibitors of dipeptidyl peptidase-IV(sitagliptin),pancreatic lipase(Orlistat),GPR119 knockout mice] were evaluated.RESULTS DGAT1 deficient mice and wildtype C57/BL6J mice werelipid challenged and levels of both active and total GLP-1 in the plasma were increased.This response was further augmented with DGAT1 inhibitor PF-04620110 treated wildtype mice.Furthermore,PF-04620110 was able to dose responsively increase GLP-1 and PYY,but blunt GIP at all doses of PF-04620110 during lipid challenge.Combination treatment of PF-04620110 and Sitagliptin in wildtype mice during a lipid challenge synergistically enhanced postprandial levels of active GLP-1.In contrast,in a combination study with Orlistat,the ability of PF-04620110 to elicit an enhanced incretin response was abrogated.To further explore this observation,GPR119 knockout mice were evaluated.In response to a lipid challenge,GPR119 knockout mice exhibited no increase in active or total GLP-1 and PYY.However,PF-04620110 was able to increase total GLP-1 and PYY in GPR119 knockout mice as compared to vehicle treated wildtype mice.CONCLUSION Collectively,these data provide some insight into the mechanism by which inhibition of DGAT1 enhances intestinal hormone release. | Benjamin S Maciejewski Tara B Manion Claire M Steppan | 2017 | World Journal of Gastrointestinal Pathophysiology2017，8，4： | 2 |
| 2 | Small-molecule inhibitors of Bcl-2 显示文摘 | Manion M K Fry J Schwartz P S | 2006 | Curr Opin Investig Drugs2006，7，12： | 1 |
| 3 | The spatial links tool: Automated mapping of habitat linkages invariegated landscapes 显示文摘 | Drielsma M Manion G Ferrier S | 2007 | Ecological Modelling2007，200，34： | 1 |
| 4 | Cellular uptake and in situ binding of a peptide agonist for calmodulin显示文摘 | Manion MK Villain M Pan ZG | 2000 | Biochem Biophys Res Commun2000，277，2： | 1 |
| 5 | 2-Methoxy antimycin reveals a unique mecha- nism for Bcl-XL inhibition 显示文摘 | SCHWARTZ P S MANION M K EMERSON C B | 2007 | Mol Cancer Ther2007，6，7： | 1 |
| 6 | Technological catastrophes: their causes and prevention 显示文摘 | MANION M EVAN W M | 2002 | Technology in Society2002，24，： | 1 |
| 7 | The electoral connection in Chinese Country-side显示文摘 | MANION M | 1996 | American Political Science Review1996，90，12： | 1 |
| 8 | Targeting Bcl-2-related proteins in cancer therapy显示文摘 | Manion M K Hockenbery D M | 2003 | Cancer Biol Ther2003，2，41： | 1 |
| 9 | Policy Implementation in the People's Republic of China: Authoritative Decisions and Individual Interests 显示文摘 | MANION M | 1991 | The Journal of Asian Studies1991，，2： | 1 |
| 10 | Fetal Microchi- merism and Women's Health: A New Paradigm 显示文摘 | Groer M W Manion M Szekeres C | 2011 | Biol Hes Nurs2011，13，4： | 1 |
| 11 | Promises and challenges of targeting Bcl-2 anti-apoptotic proteins for cancer therapy 显示文摘 | O'Neill J Manion M Schwartz P | 2004 | Biochim Biophys Acta2004，1705，1： | 1 |
| 12 | Policy implementation in the People's Re- public of China: Authoritative decisions versus individ- ual interests显示文摘 | Manion M | 1991 | The Journal of Asian Studies1991，50，2： | 1 |
| 13 | Combination chemotherapy for human immunodeficiency virus-1显示文摘 | Hirsch M S | 1997 | Am J Med1997，102，5： | 1 |
| 14 | Arc stability of electronegative gases显示文摘 | Manion J P Philosop J A Robinson M B | 1967 | IEEE Transactions on ElectricaL Insulation1967，2，1： | 1 |
| 15 | 'Good Types' authoritarian elections:the seleetoral eonnection in Chinese Local Congresses 显示文摘 | MANION M | 2014 | Comparative Political Studies2014，，10： | 1 |
| 16 | Chinese democratization in perspective:Electorates and selectorates at the township level显示文摘 | Manion M | | 0，，： | 1 |
| 17 | Antifungal compounds in aspen:effect of water stress显示文摘 | Kruger B M Manion P D | 1994 | Canadian Journal of Botany1994，72，4： | 1 |
| 18 | Stress im- pairs alpha ( 1 A ) adreno,eptor-mdiated noradn'energic facilitation of GABAergic transmission in lhe lmsolat-ral amygdala 显示文摘 | Braga M F Aroniadu-Anderjaska V Manion S T e al | 2004 | Neunpsy- chopharmacotogy2004，29，1： | 1 |
| 19 | Corruption and corruption control: more of the same in 1996显示文摘 | Manion M | 1997 | China Review1997，，： | 1 |
| 20 | Promises and challenges of targeting Bcl-2 anti-apoptotic proteins for cancer therapy 显示文摘 | O'Neill J Manion M Schwartz P | 2004 | Biochim Biophys Acta2004，1705，1： | 1 |
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