RalA controls glucose homeostasis by regulating glucose uptake in brown fat

Yuliya Skorobogatko, Morgan Dragan, Claudia Cordon, Shannon M. Reilly, Chao Wei Hung, Wenmin Xia, Peng Zhao, Martina Wallace, Denise E. Lackey, Xiao Wei Chen, Olivia Osborn, Juliane G. Bogner-Strauss, Dan Theodorescu, Christian M. Metallo, Jerrold M. Olefsky, Alan R. Saltiel

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7819-7824
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number30
DOIs
StatePublished - Jul 24 2018
Externally publishedYes

Keywords

  • Glut4
  • GTPase
  • insulin
  • Ral inhibitors
  • RalGAP

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'RalA controls glucose homeostasis by regulating glucose uptake in brown fat'. Together they form a unique fingerprint.

Cite this