title: Insulin responsiveness of glucose transporter 4 in 3T3-L1 cells depends on the presence of sortilin.
abstract: Insulin-dependent translocation of glucose transporter 4 (Glut4) to the plasma membrane of fat and skeletal muscle cells plays the key role in postprandial clearance of blood glucose. Glut4 represents the major cell-specific component of the insulin-responsive vesicles (IRVs). It is not clear, however, whether the presence of Glut4 in the IRVs is essential for their ability to respond to insulin stimulation. We prepared two lines of 3T3-L1 cells with low and high expression of myc7-Glut4 and studied its translocation to the plasma membrane upon insulin stimulation, using fluorescence-assisted cell sorting and cell surface biotinylation. In undifferentiated 3T3-L1 preadipocytes, translocation of myc7-Glut4 was low regardless of its expression levels. Coexpression of sortilin increased targeting of myc7-Glut4 to the IRVs, and its insulin responsiveness rose to the maximal levels observed in fully differentiated adipocytes. Sortilin ectopically expressed in undifferentiated cells was translocated to the plasma membrane regardless of the presence or absence of myc7-Glut4. AS160/TBC1D4 is expressed at low levels in preadipocytes but is induced in differentiation and provides an additional mechanism for the intracellular retention and insulin-stimulated release of Glut4.
authors: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118.
authors: Guanrong
authors: G
authors: Huang
authors: Dana
authors: D
authors: Buckler-Pena
authors: Tessa
authors: T
authors: Nauta
authors: Maneet
authors: M
authors: Singh
authors: Agnes
authors: A
authors: Asmar
authors: Jun
authors: J
authors: Shi
authors: Ju Youn
authors: JY
authors: Kim
authors: Konstantin V
authors: KV
authors: Kandror
mesh_terms: D041721:3T3-L1 Cells; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D016271:Proto-Oncogene Proteins c-myc; D000099183:Sortilin
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