title: GLP-1 and GLP-2 as yin and yang of intestinal lipoprotein production: evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin-resistant states.
abstract: The glucagon-like peptides (GLP-1 and GLP-2) are processed from the proglucagon polypeptide and secreted in equimolar amounts but have opposite effects on chylomicron (CM) production, with GLP-1 significantly reducing and GLP-2 increasing postprandial chylomicronemia. In the current study, we evaluated the apparent paradoxical roles of GLP-1 and GLP-2 under physiological conditions in the Syrian golden hamster, a model with close similarity to humans in terms of lipoprotein metabolism. A short (30-min) intravenous infusion of GLP-2 resulted in a marked increase in postprandial apolipoprotein B48 (apoB48) and triglyceride (TG) levels in the TG-rich lipoprotein (TRL) fraction, whereas GLP-1 infusion decreased lipid absorption and levels of TRL-TG and apoB48. GLP-1 and GLP-2 coinfusion resulted in net increased lipid absorption and an increase in TRL-TG and apoB48. However, prolonged (120-min) coinfusion of GLP-1 and GLP-2 decreased postprandial lipemia. Blocking dipeptidyl peptidase-4 activity resulted in decreased postprandial lipemia. Interestingly, fructose-fed, insulin-resistant hamsters showed a more pronounced response, including possible hypersensitivity to GLP-2 or reduced sensitivity to GLP-1. In conclusion, under normal physiological conditions, the actions of GLP-2 predominate; however, when GLP-1 activity is sustained, the hypolipidemic action of GLP-1 predominates. Pharmacological inhibition of GLP-1 degradation tips the balance toward an inhibitory effect on intestinal production of atherogenic CM particles.
authors.affiliation: Molecular Structure and Function, Research Institute, The Hospital for Sick Children, and Department of Biochemistry and Laboratory Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gustavo J
authors.initials: GJ
authors.lastname: Hein
authors.forename: Chris
authors.initials: C
authors.lastname: Baker
authors.forename: Joanne
authors.initials: J
authors.lastname: Hsieh
authors.forename: Sarah
authors.initials: S
authors.lastname: Farr
authors.forename: Khosrow
authors.initials: K
authors.lastname: Adeli
mesh_terms: D000818:Animals; D053283:Apolipoprotein B-48 / Q000096:biosynthesis; D002914:Chylomicrons / Q000096:biosynthesis / Q000187:drug effects; D006224:Cricetinae; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology; D005632:Fructose / Q000008:administration & dosage; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage*; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage*; D006949:Hyperlipidemias / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D007408:Intestinal Absorption / Q000187:drug effects; D007422:Intestines / Q000187:drug effects*; D050356:Lipid Metabolism / Q000187:drug effects; D008074:Lipoproteins / Q000096:biosynthesis*; D008297:Male; D008647:Mesocricetus; D019518:Postprandial Period / Q000187:drug effects*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D053283:Apolipoprotein B-48; D002914:Chylomicrons; D054873:Dipeptidyl-Peptidase IV Inhibitors; D053767:Glucagon-Like Peptide 2; D008074:Lipoproteins; D014280:Triglycerides; D005632:Fructose; D052216:Glucagon-Like Peptide 1