Reports from Pfizer Describe Recent Advances in Hormones (Pharmacological inhibition of diacylglycerol acyltransferase-1 and insights into postprandial gut peptide secretion)
By a News Reporter-Staff News Editor at Drug Week -- Current study results on Drugs and Therapies - Hormones have been published. According to news originating from Cambridge, Massachusetts, by NewsRx correspondents, research stated, "To examine the role that enzyme Acyl-CoA:diacylglycerol acyltransferase-1 (DGAT1) plays in postprandial gut peptide secretion and signaling. The standard experimental paradigm utilized to evaluate the incretin response was a lipid challenge."
Our news journalists obtained a quote from the research from Pfizer, "Following a lipid challenge, plasma was collected 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. DGAT1 deficient mice and wildtype C57/BL6J mice were lipid 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."
According to the news editors, the research concluded: "Collectively, these data provide some insight into the mechanism by which inhibition of DGAT1 enhances intestinal hormone release."
For more information on this research see: Pharmacological inhibition of diacylglycerol acyltransferase-1 and insights into postprandial gut peptide secretion. World Journal of Gastrointestinal Pathophysiology, 2017;8(4):161-175 (see also Drugs and Therapies - Hormones).
The news correspondents report that additional information may be obtained from B.S. Maciejewski, Pfizer Worldwide Research and Development, Cardiovascular and Metabolic Diseases Research Unit, Cambridge, MA 02139, United States. Additional authors for this research include T.B. Manion and C.M Steppan.
The direct object identifier (DOI) for that additional information is: https://doi.org/10.4291/wjgp.v8.i4.161. This DOI is a link to an online electronic document that is either free or for purchase, and can be your direct source for a journal article and its citation.
Keywords for this news article include: Hormones, Peptides, Proteins, Cambridge, Incretins, Proteomics, Pharmacology, Massachusetts, United States, Acyltransferases, Drugs and Therapies, Enzymes and Coenzymes, North and Central America.
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