Repression of GLUT4 expression by the endoplasmic reticulum stress response in 3T3-L1 adipocytes.
Expression of GLUT4 is decreased in adipocytes in obesity and type 2 diabetes, contributing to the insulin resistance of these states. Recent investigations suggest a role for activation of the ER stress response in the pathophysiology of type 2 diabetes. We investigated activation of the ER stress response in 3T3-L1 adipocytes. We show that activation of the ER stress response decreased GLUT4 expression at the level of gene transcription. Activation of the ER stress response also increased the expression of CHOP10, an inhibitor of the activity and expression of C/EBPalpha. As expected, activation of the ER stress response decreased expression of C/EBPalpha, an activator of GLUT4 expression, providing a mechanism to account for the repression of GLUT4 by ER stress activation. Our studies identify repression of GLUT4 expression as another potential mechanism for obesity-induced activation of the ER stress response to contribute to the insulin resistance of obesity.
Miller
Ryan S
RS
Department of Pediatrics, Johns Hopkins University School of Medicine, 200 North Wolfe Street, Baltimore, MD 21287, USA.
Diaczok
Daniel
D
Department of Pediatrics, Johns Hopkins University School of Medicine, 200 North Wolfe Street, Baltimore, MD 21287, USA.
Cooke
David W
DW
Department of Pediatrics, Johns Hopkins University School of Medicine, 200 North Wolfe Street, Baltimore, MD 21287, USA. Electronic address: dcooke@jhmi.edu.
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D051379:Mice; D009765:Obesity; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011489:Protein Denaturation; D051742:Transcription Factor CHOP / Q000378:metabolism
D022763:CCAAT-Enhancer-Binding Protein-alpha; C497250:Ddit3 protein, mouse; D051275:Glucose Transporter Type 4; D007328:Insulin; C495693:Slc2a4 protein, mouse; D051742:Transcription Factor CHOP; D046988:Proteasome Endopeptidase Complex
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