title: Gut Peptides Are Novel Regulators of Intestinal Lipoprotein Secretion: Experimental and Pharmacological Manipulation of Lipoprotein Metabolism.
abstract: Individuals with metabolic syndrome and frank type 2 diabetes are at increased risk of atherosclerotic cardiovascular disease, partially due to the presence of lipid and lipoprotein abnormalities. In these conditions, the liver and intestine overproduce lipoprotein particles, exacerbating the hyperlipidemia of fasting and postprandial states. Incretin-based, antidiabetes therapies (i.e., glucagon-like peptide [GLP]-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) have proven efficacy for the treatment of hyperglycemia. Evidence is accumulating that these agents also improve fasting and postprandial lipemia, the latter more significantly than the former. In contrast, the gut-derived peptide GLP-2, cosecreted from intestinal L cells with GLP-1, has recently been demonstrated to enhance intestinal lipoprotein release. Understanding the roles of these emerging regulators of intestinal lipoprotein secretion may offer new insights into the regulation of intestinal lipoprotein assembly and secretion and provide new opportunities for devising novel strategies to attenuate hyperlipidemia, with the potential for cardiovascular disease reduction.
authors.affiliation: Departments of Medicine and Physiology and Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Changting
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Departments of Medicine and Physiology and Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Satya
authors.initials: S
authors.lastname: Dash
authors.affiliation: Departments of Medicine and Physiology and Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgantini
authors.affiliation: Program in Molecular Structure & Function, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Khosrow
authors.initials: K
authors.lastname: Adeli
authors.affiliation: Departments of Medicine and Physiology and Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada gary.lewis@uhn.ca.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Lewis
mesh_terms: D000818:Animals; D053283:Apolipoprotein B-48 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1 / Q000502:physiology*; D053767:Glucagon-Like Peptide 2 / Q000502:physiology*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D054795:Incretins / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D018027:Receptors, Glucagon / Q000819:agonists; D014280:Triglycerides / Q000378:metabolism
chemical_list: D053283:Apolipoprotein B-48; D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D008074:Lipoproteins; D018027:Receptors, Glucagon; D014280:Triglycerides; D052216:Glucagon-Like Peptide 1