title: Apolipoprotein A-IV improves glucose homeostasis by enhancing insulin secretion.
abstract: Apolipoprotein A-IV (apoA-IV) is secreted by the small intestine in response to fat absorption. Here we demonstrate a potential role for apoA-IV in regulating glucose homeostasis. ApoA-IV-treated isolated pancreatic islets had enhanced insulin secretion under conditions of high glucose but not of low glucose, suggesting a direct effect of apoA-IV to enhance glucose-stimulated insulin release. This enhancement involves cAMP at a level distal to Ca(2+) influx into the β cells. Knockout of apoA-IV results in compromised insulin secretion and impaired glucose tolerance compared with WT mice. Challenging apoA-IV(-/-) mice with a high-fat diet led to fasting hyperglycemia and more severe glucose intolerance associated with defective insulin secretion than occurred in WT mice. Administration of exogenous apoA-IV to apoA-IV(-/-) mice improved glucose tolerance by enhancing insulin secretion in mice fed either chow or a high-fat diet. Finally, we demonstrate that exogenous apoA-IV injection decreases blood glucose levels and stimulates a transient increase in insulin secretion in KKAy diabetic mice. These results suggest that apoA-IV may provide a therapeutic target for the regulation of glucose-stimulated insulin secretion and treatment of diabetes.
authors.affiliation: Departments of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Alison B
authors.initials: AB
authors.lastname: Kohan
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Kindel
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Corbin
authors.forename: Craig S
authors.initials: CS
authors.lastname: Nunemaker
authors.forename: Silvana
authors.initials: S
authors.lastname: Obici
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
authors.forename: W Sean
authors.initials: WS
authors.lastname: Davidson
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
mesh_terms: D000818:Animals; D001054:Apolipoproteins A / Q000235:genetics / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D051379:Mice; D018345:Mice, Knockout
chemical_list: D001054:Apolipoproteins A; D007328:Insulin; C022205:apolipoprotein A-IV; D005947:Glucose