Differentiated 3T3L1 adipocytes are composed of heterogenous cell populations with distinct receptor tyrosine kinase signaling properties.
Various studies have demonstrated that the platelet-derived growth factor (PDGF) receptor in adipocytes can activate PI 3-kinase activity without affecting insulin-responsive glucose transporter (GLUT4) translocation. To investigate this phenomenon of receptor signaling specificity, we utilized single cell analysis to determine the cellular distribution and signaling properties of PDGF and insulin in differentiated 3T3L1 adipocytes. The insulin receptor was highly expressed in a large percentage of the cell population (>95%) that also expressed caveolin 2 and GLUT4 with very low levels of the PDGF receptor. In contrast, the PDGF receptor was only expressed in approximately 10% of the differentiated 3T3L1 cell population with relatively low levels of the insulin receptor, caveolin 2, and GLUT4. Consistent with this observation, insulin stimulated the phosphorylation of Akt in the caveolin 2- and GLUT4-positive cells, whereas PDGF primarily stimulated Akt phosphorylation in the caveolin 2- and GLUT4-negative cell population. Furthermore, transfection of the PDGF receptor in the insulin receptor-, GLUT4-, and caveolin 2-positive cells resulted in the ability of PDGF to stimulate GLUT4 translocation. These data demonstrate that differentiated 3T3L1 adipocytes are not a homogeneous population of cells, and the lack of PDGF receptor expression in the GLUT4-positive cell population accounts for the inability of the endogenous PDGF receptor to activate GLUT4 translocation.
Shigematsu
S
S
Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa 52242, USA.
Miller
S L
SL
Pessin
J E
JE
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D051275:Glucose Transporter Type 4; D006801:Humans; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D020033:Protein Isoforms / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction
D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; C495692:SLC2A4 protein, human; C495693:Slc2a4 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor