RalA controls glucose homeostasis by regulating glucose uptake in brown fat.

Autor:	Skorobogatko Y; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093.; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109., Dragan M; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093., Cordon C; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109., Reilly SM; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093.; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109., Hung CW; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093., Xia W; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093.; Institute of Biochemistry, Graz University of Technology, 8010 Graz, Austria., Zhao P; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093.; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109., Wallace M; Jacobs School of Engineering, University of California, San Diego, La Jolla, CA 92093., Lackey DE; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093., Chen XW; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109., Osborn O; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093., Bogner-Strauss JG; Institute of Biochemistry, Graz University of Technology, 8010 Graz, Austria., Theodorescu D; Department of Surgery, University of Colorado, Aurora, CO 80045., Metallo CM; Jacobs School of Engineering, University of California, San Diego, La Jolla, CA 92093., Olefsky JM; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093., Saltiel AR; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093; asaltiel@ucsd.edu.; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Jul 24; Vol. 115 (30), pp. 7819-7824. Date of Electronic Publication: 2018 Jun 18.
DOI:	10.1073/pnas.1801050115
Abstrakt:	Insulin increases glucose uptake into adipose tissue and muscle by increasing trafficking of the glucose transporter Glut4. In cultured adipocytes, the exocytosis of Glut4 relies on activation of the small G protein RalA by insulin, via inhibition of its GTPase activating complex RalGAP. Here, we evaluate the role of RalA in glucose uptake in vivo with specific chemical inhibitors and by generation of mice with adipocyte-specific knockout of RalGAPB. RalA was profoundly activated in brown adipose tissue after feeding, and its inhibition prevented Glut4 exocytosis. RalGAPB knockout mice with diet-induced obesity were protected from the development of metabolic disease due to increased glucose uptake into brown fat. Thus, RalA plays a crucial role in glucose transport in adipose tissue in vivo. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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