A liver HIF-2α/IRS2 pathway sensitizes hepatic insulin signaling and is modulated by VEGF inhibition Kevin Wei1*, Stephanie M. Piecewicz1*, Lisa M. McGinnis1*, Cullen M. Taniguchi2, Stanley J. Wiegand3, Keith Anderson3, Carol W-M. Chan1, Kimberly X. Mulligan4, David Kuo1, Jenny Yuan1, Mario Vallon1, Lori Morton3, Etienne Lefai5, M. Celeste Simon6, Jacquelyn J. Maher7, Gilles Mithieux8, Fabienne Rajas8, Justin Annes9, Owen P. McGuinness4, Gavin Thurston3, Amato J. Giaccia2, and Calvin J. Kuo1 1
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Divisions of Hematology, Radiation Oncology and Endocrinology and Metabolism, Stanford University School of Medicine, Stanford, California 94305, USA. 3 Regeneron Pharmaceuticals, Incorporated, Tarrytown, New York, 10591, USA. 4
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville TN 37232, USA. 5 INSERM U 1060, INRA 1235, Universite de Lyon, Faculté de Médecine Lyon Sud - BP12, 69921 OULLINS Cedex, France. 6 Abramson Family Cancer Research Institute, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, USA. 7 UCSF Liver Center, San Francisco General Hospital, 1001 Potrero Ave. Building 40, Room 4102, San Francisco, CA 94110 8 Inserm U855/Université Lyon, Faculté Lyon Est Laennec, 7 rue Guillaume Paradin, 69372 Lyon cedex 08, France * denotes equal contributions Corresponding author: Calvin J. Kuo, Division of Hematology, Stanford University School of Medicine, Stanford, California 94305, USA.
[email protected]
Supplementary Information Including Supplementary Figures 1-8
Supplementary Figure 1 a
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Supplementary Figure 1. a-f. The AUC values from the GTT and ITT studies from sFlt1, sFlk1 and aflibercept-treated mice in Figure 1 are presented. g. 8-10 week old db/db mice received i.p. injection of the anti-VEGF mAb B20.4.1.1 for 14 days at 5mg/kg 3x/week followed by GTT. h. C57Bl/6 mice (n=5) received anti VEGFR2 mAb DC101 s.c. 40 mg/kg 2x/week for 14 days followed by GTT. *= p