title: ATM Regulates Adipocyte Differentiation and Contributes to Glucose Homeostasis.
abstract: Ataxia-telangiectasia (A-T) patients occasionally develop diabetes mellitus. However, only limited attempts have been made to gain insight into the molecular mechanism of diabetes mellitus development in A-T patients. We found that Atm-/-mice were insulin resistant and possessed less subcutaneous adipose tissue as well as a lower level of serum adiponectin than Atm+/+mice. Furthermore, in vitro studies revealed impaired adipocyte differentiation in Atm-/-cells caused by the lack of induction of C/EBPα and PPARγ, crucial transcription factors involved in adipocyte differentiation. Interestingly, ATM was activated by stimuli that induced differentiation, and the binding of ATM to C/EBPβ and p300 was involved in the transcriptional regulation of C/EBPα and adipocyte differentiation. Thus, our study sheds light on the poorly understood role of ATM in the pathogenesis of glucose intolerance in A-T patients and provides insight into the role of ATM in glucose metabolism.
authors: Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Electronic address: m.takagi.ped@tmd.ac.jp.
authors: Masatoshi
authors: M
authors: Takagi
authors: Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Medical Business Unit, Sony Corporation, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors: Hatsume
authors: H
authors: Uno
authors: Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors: Rina
authors: R
authors: Nishi
authors: Section of Biochemistry, National Institute for Longevity Sciences, NCGG, 36-3 Gengo, Moriokacho, Obu, Aichi 474-8522, Japan.
authors: Masataka
authors: M
authors: Sugimoto
authors: Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors: Setsuko
authors: S
authors: Hasegawa
authors: Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors: Jinhua
authors: J
authors: Piao
authors: Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Ohkura, Setagaya-ku, Tokyo 157-0074, Japan.
authors: Norimasa
authors: N
authors: Ihara
authors: Department of Molecular Endocrinology and Metabolism, Graduate School of Medicine, Tokyo Medical and Dental University, Japan Science and Technology Agency, CREST, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors: Sayaka
authors: S
authors: Kanai
authors: Department of Medicine, Metabolism & Endocrinology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors: Saori
authors: S
authors: Kakei
authors: Department of Medicine, Metabolism & Endocrinology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors: Yoshifumi
authors: Y
authors: Tamura
authors: Department of Organ Network and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan Science and Technology Agency, PRESTO, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors: Takayoshi
authors: T
authors: Suganami
authors: Laboratory of Molecular Nutrition, Graduate School of Environmental and Life Science, Kyoto Prefectural University, Hangicho 1-5, Shimogamo, Kyotoshi, Kyoto 606-8522, Japan.
authors: Yasutomi
authors: Y
authors: Kamei
authors: Department of Pediatrics and Adolescent Medicine, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Toshiaki
authors: T
authors: Shimizu
authors: Section of Biochemistry, National Institute for Longevity Sciences, NCGG, 36-3 Gengo, Moriokacho, Obu, Aichi 474-8522, Japan.
authors: Akio
authors: A
authors: Yasuda
authors: Department of Molecular Endocrinology and Metabolism, Graduate School of Medicine, Tokyo Medical and Dental University, Japan Science and Technology Agency, CREST, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors: Yoshihiro
authors: Y
authors: Ogawa
authors: Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors: Shuki
authors: S
authors: Mizutani