title: The role of apolipoprotein A-IV in regulating glucagon-like peptide-1 secretion.
abstract: Both glucagon-like peptide-1 (GLP-1) and apolipoprotein A-IV (apoA-IV) are produced from the gut and enhance postprandial insulin secretion. This study investigated whether apoA-IV regulates nutrient-induced GLP-1 secretion and whether apoA-IV knockout causes compensatory GLP-1 release. Using lymph-fistula-mice, we first determined lymphatic GLP-1 secretion by administering apoA-IV before an intraduodenal Ensure infusion. apoA-IV changed neither basal nor Ensure-induced GLP-1 secretion relative to saline administration. We then assessed GLP-1 in apoA-IV-/- and wild-type (WT) mice administered intraduodenal Ensure. apoA-IV-/- mice had comparable lymph flow, lymphatic triglyceride, glucose, and protein outputs as WT mice. Intriguingly, apoA-IV-/- mice had higher lymphatic GLP-1 concentration and output than WT mice 30 min after Ensure administration. Increased GLP-1 was also observed in plasma of apoA-IV-/- mice at 30 min. apoA-IV-/- mice had comparable total gut GLP-1 content relative to WT mice under fasting, but a lower GLP-1 content 30 min after Ensure administration, suggesting that more GLP-1 was secreted. Moreover, an injection of apoA-IV protein did not reverse the increased GLP-1 secretion in apoA-IV-/- mice. Finally, we assessed gene expression of GLUT-2 and the lipid receptors, including G protein-coupled receptor (GPR) 40, GPR119, and GPR120 in intestinal segments. GLUT-2, GPR40 and GPR120 mRNAs were unaltered by apoA-IV knockout. However, ileal GPR119 mRNA was significantly increased in apoA-IV-/- mice. GPR119 colocalizes with GLP-1 in ileum and stimulates GLP-1 secretion by sensing OEA, lysophosphatidylcholine, and 2-monoacylglycerols. We suggest that increased ileal GPR119 is a potential mechanism by which GLP-1 secretion is enhanced in apoA-IV-/- mice.
authors: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio; and.
authors: Fei
authors: F
authors: Wang
authors: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio; and.
authors: Qing
authors: Q
authors: Yang
authors: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio; and.
authors: Sarah
authors: S
authors: Huesman
authors: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio; and.
authors: Min
authors: M
authors: Xu
authors: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio; and.
authors: Xiaoming
authors: X
authors: Li
authors: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio; and.
authors: Danwen
authors: D
authors: Lou
authors: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, Ohio.
authors: Stephen C
authors: SC
authors: Woods
authors: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio; and.
authors: Corina
authors: C
authors: Marziano
authors: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio; and tsopp@ucmail.uc.edu.
authors: Patrick
authors: P
authors: Tso
mesh_terms: D000818:Animals; D001054:Apolipoproteins A / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007082:Ileum / Q000378:metabolism; D054795:Incretins / Q000378:metabolism; D008196:Lymph / Q000737:chemistry / Q000378:metabolism; D008208:Lymphatic System / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism
chemical_list: D001054:Apolipoproteins A; D054795:Incretins; D043562:Receptors, G-Protein-Coupled; C022205:apolipoprotein A-IV; D052216:Glucagon-Like Peptide 1
keywords: GLP-1; GPR119; apoA-IV; enteroinsular axis; glucose homeostasis