title: ADP-ribosylation factor 6 (ARF6) defines two insulin-regulated secretory pathways in adipocytes.
abstract: ADP-ribosylation factor 6 (ARF6) appears to play an essential role in the endocytic/recycling pathway in several cell types. To determine whether ARF6 is involved in insulin-regulated exocytosis, 3T3-L1 adipocytes were infected with recombinant adenovirus expressing wild-type ARF6 or an ARF6 dominant negative mutant (D125N) that encodes a protein with nucleotide specificity modified from guanine to xanthine. Overexpression of these ARF6 proteins affected neither basal nor insulin-regulated glucose uptake in 3T3-L1 adipocytes, nor did it affect the subcellular distribution of Glut1 or Glut4. In contrast, the secretion of adipsin, a serine protease specifically expressed in adipocytes, was increased by the expression of wild-type ARF6 and was inhibited by the expression of D125N. These results indicate a requirement for ARF6 in basal and insulin-regulated adipsin secretion but not in glucose transport. Our results suggest the existence of at least two distinct pathways that undergo insulin-stimulated exocytosis in 3T3-L1 adipocytes, one for adipsin release and one for glucose transporter translocation.
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: C Z
authors.initials: CZ
authors.lastname: Yang
authors.forename: M
authors.initials: M
authors.lastname: Mueckler
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors; D017667:Adipocytes / Q000378:metabolism*; D019943:Amino Acid Substitution; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D004705:Endocytosis / Q000187:drug effects*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D009154:Mutation; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000089982:ADP-Ribosylation Factor 6; D007004:Hypoglycemic Agents; D007328:Insulin; D019204:GTP-Binding Proteins; D020727:ADP-Ribosylation Factors; C000715727:Arf6 protein, mouse; D005947:Glucose