Copyright
©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Nov 15, 2017; 8(4): 161-175
Published online Nov 15, 2017. doi: 10.4291/wjgp.v8.i4.161
Published online Nov 15, 2017. doi: 10.4291/wjgp.v8.i4.161
Pharmacological inhibition of diacylglycerol acyltransferase-1 and insights into postprandial gut peptide secretion
Benjamin S Maciejewski, Tara B Manion, Claire M Steppan, Pfizer Worldwide Research and Development, Cardiovascular and Metabolic Diseases Research Unit, Cambridge, MA 02139, United States
Claire M Steppan, Pfizer Inc., Groton, CT 06340, United States
Author contributions: Maciejewski BS, Manion TB and Steppan CM substantially contributed to the conception and design of the study, analysis and interpretation of data; Maciejewski BS and Manion TB contributed to the study acquisition; Maciejewski BS and Steppan CM drafted the article and made critical revisions related to the intellectual content of the manuscript and approved the final version of the article published.
Supported by Pfizer Inc.
Institutional review board statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Pfizer Inc.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Pfizer Inc. (IACUC protocol number: GTN-16169-2011).
Conflict-of-interest statement: All authors were employees of Pfizer Inc. during the conduct of these studies. To the best of our knowledge, no conflict of interest exists.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Claire M Steppan, PhD, Associate Research Fellow, Pfizer Inc., Eastern Point Road, Groton, CT 06340, United States. claire.m.steppan@pfizer.com
Telephone: +1-860-4413774
Received: January 29, 2017
Peer-review started: February 13, 2017
First decision: July 10, 2017
Revised: July 25, 2017
Accepted: September 4, 2017
Article in press: September 5, 2017
Published online: November 15, 2017
Processing time: 287 Days and 13.4 Hours
Peer-review started: February 13, 2017
First decision: July 10, 2017
Revised: July 25, 2017
Accepted: September 4, 2017
Article in press: September 5, 2017
Published online: November 15, 2017
Processing time: 287 Days and 13.4 Hours
Core Tip
Core tip: Pharmacological Inhibition of diacylglycerol acyltransferase-1 (DGAT1) and insights into postprandial gut peptide secretion” describes studies that evaluate the effects of loss of DGAT1 function either pharmacologically or genetically on the incretin response. We demonstrate a synergistic effect on the incretin response with the combination of a DGAT1 inhibitor and sitagliptin, a dipeptidyl peptidase-IV inhibitor. Additional studies performed address the molecular mechanism by with pharmacological inhibition of DGAT1 results in increased gut peptide secretion. These data provide insight into the role of DGAT1 in the intestinal hormone release and its potential as a drug target for the treatment of type 2 diabetes.