1 Role of UCP-2 Up-regulation and TG accumulation in Impaired Glucose- stimulated Insulin Secretion in a β-Cell Lipotoxicity Model Overexpressing SREBP-1c Tokuyuki Yamashita 1 , Kazuhiro Eto 1, 2 , Yukiko Okazaki 1, 2 , Shigeo Yamashita 1# , Toshimasa Yamauchi 1, 2 , Nobuo Sekine 1 , Ryozo Nagai 3 , Mitsuhiko Noda 2, 4# , and Takashi Kadowaki 1, 2 1 Department of Metabolic Diseases and 3 Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan 2 CREST of Japan Science and Technology Corporation, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan 4 Institute for Diabetes Care and Research, Asahi Life Foundation, 1-6-1 Marunouchi, Chiyoda-ku, Tokyo 100-0005, Japan # Present address Toranomon Hospital, 2-2-2 Toranomon Minato-ku, Tokyo 105-8470, Japan. Running Title: Impaired insulin secretion in a β-cell lipotoxicity model. Address correspondence to: Takashi Kadowaki M.D., Ph.D., Professor Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan Phone: +81 (3) 5800-8818, Fax: +81 (3) 5689-7209, E-mail: kadowaki-3im@h.u-tokyo.ac.jp Key words: Insulin, β-cell, Lipotoxicity, SREBP-1c, UCP-2, Triglyceride, AICAR Endocrinology. First published April 1, 2004 as doi:10.1210/en.2003-1602 Copyright (C) 2004 by The Endocrine Society