title: ApoA-IV improves insulin sensitivity and glucose uptake in mouse adipocytes via PI3K-Akt Signaling.
abstract: Insulin resistance is a risk factor for type 2 diabetes mellitus. We investigated the effect of ApoA-IV on glucose uptake in the adipose and muscle tissues of mice and cultured 3T3-L1 adipocytes. We found that treatment with ApoA-IV lowered fasting blood glucose in both WT and diabetic KKAy mice by increasing glucose uptake in cardiac muscle, white adipose tissue, and brown adipose tissue through a mechanism that was partially insulin independent. Cell culture experiments showed that ApoA-IV improved glucose uptake in adipocytes in the absence of insulin by upregulating GLUT4 translocation by PI3K mediated activation of Akt signaling pathways. Considering our previous finding that ApoA-IV treatment enhanced pancreatic insulin secretion, these results suggests that ApoA-IV acts directly upon adipose tissue to improve glucose uptake and indirectly via insulin signaling. Our findings warrant future studies to identify the receptor for ApoA-IV and the downstream targets of PI3K-Akt signaling that regulate glucose uptake in adipocytes as potential therapeutic targets for treating insulin resistance.
authors.affiliation: National Local Joint Engineering Research Centre of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, 157 W 5th Rd, Xincheng, Xi'an 710004, China.|Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, 2180 E. Galbraith Road, Cincinnati 45237-0507, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, 2180 E. Galbraith Road, Cincinnati 45237-0507, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, 2180 E. Galbraith Road, Cincinnati 45237-0507, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, 2180 E. Galbraith Road, Cincinnati 45237-0507, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Howles
authors.affiliation: Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, 2180 E. Galbraith Road, Cincinnati 45237-0507, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001054:Apolipoproteins A / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D001054:Apolipoproteins A; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D047428:Protein Kinase Inhibitors; C022205:apolipoprotein A-IV; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D000077191:Wortmannin