title: Exenatide, a glucagon-like peptide-1 receptor agonist, acutely inhibits intestinal lipoprotein production in healthy humans.
abstract: OBJECTIVE
  Incretin-based therapies for the treatment of type 2 diabetes mellitus improve plasma lipid profiles and postprandial lipemia, but their exact mechanism of action remains unclear. Here, we examined the acute effect of the glucagon-like peptide-1 receptor agonist, exenatide, on intestinal and hepatic triglyceride-rich lipoprotein production and clearance in healthy humans.
  
  
  RESULTS
  Fifteen normolipidemic, normoglycemic men underwent 2 studies each (SC 10 μg exenatide versus placebo), 4 to 6 weeks apart, in random order, in which triglyceride-rich lipoprotein particle kinetics were examined with a primed, constant infusion of deuterated leucine and analyzed by multicompartmental modeling under pancreatic clamp conditions. A fed state was maintained during each study by infusing a high-fat, mixed macronutrient, liquid formula at a constant rate directly into the duodenum via a nasoduodenal tube. Exenatide significantly suppressed the plasma concentration and production rate of triglyceride-rich lipoprotein-apolipoprotein B-48, but not of triglyceride-rich lipoprotein-apolipoprotein B-100.
  
  
  CONCLUSIONS
  These results suggest a possible direct effect of exenatide on intestinal lipoprotein particle production, independent of changes in weight gain and satiety as seen in long-term studies and independent of changes in gastric emptying. This finding expands our understanding of the effects of exenatide in metabolic regulation beyond its primary therapeutic role in regulation of glucose homeostasis. Clinical Trial Registration- URL: http://www.clinicaltrials.gov, NCT01056549.
authors.affiliation: Departments of Medicine and Physiology, Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada.
authors.forename: Changting
authors.initials: C
authors.lastname: Xiao
authors.forename: Robert H J
authors.initials: RH
authors.lastname: Bandsma
authors.forename: Satya
authors.initials: S
authors.lastname: Dash
authors.forename: Linda
authors.initials: L
authors.lastname: Szeto
authors.forename: Gary F
authors.initials: GF
authors.lastname: Lewis
mesh_terms: D000328:Adult; D053299:Apolipoprotein B-100 / Q000097:blood; D053283:Apolipoprotein B-48 / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D015536:Down-Regulation; D000077270:Exenatide; D005934:Glucagon / Q000097:blood; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009864:Ontario; D010455:Peptides / Q000008:administration & dosage*; D019518:Postprandial Period; D018027:Receptors, Glucagon / Q000819:agonists* / Q000378:metabolism; D012016:Reference Values; D014280:Triglycerides / Q000097:blood*; D014688:Venoms / Q000008:administration & dosage*
chemical_list: D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D001786:Blood Glucose; D002096:C-Peptide; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D018027:Receptors, Glucagon; D014280:Triglycerides; D014688:Venoms; D005934:Glucagon; D000077270:Exenatide