RalA controls glucose homeostasis by regulating glucose uptake in brown fat

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 ev...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2018-07, Vol.115 (30), p.7819-7824
Main Authors: Skorobogatko, Yuliya, Dragan, Morgan, Cordon, Claudia, Reilly, Shannon M., Hung, Chao-Wei, Xia, Wenmin, Zhao, Peng, Wallace, Martina, Lackey, Denise E., Chen, Xiao-Wei, 陈晓伟, Osborn, Olivia, Bogner-Strauss, Juliane G., Theodorescu, Dan, Metallo, Christian M., Olefsky, Jerrold M., Saltiel, Alan R.
Format: Article
Language:English
Subjects:
3T3-L1 Cells
Adipocytes
Adipose tissue
Adipose tissue (brown)
Adipose Tissue, Brown - metabolism
Adipose Tissue, Brown - pathology
Animals
Biological Sciences
Exocytosis
Gene Deletion
Glucose
Glucose - genetics
Glucose - metabolism
Glucose transport
Glucose transporter
Glucose Transporter Type 4 - genetics
Glucose Transporter Type 4 - metabolism
GTPase-Activating Proteins - genetics
GTPase-Activating Proteins - metabolism
Guanosine triphosphatases
Homeostasis
Inhibition
Insulin
Insulin resistance
Mice
Mice, Knockout
Muscles
Obesity
Organic chemistry
Proteins
ral GTP-Binding Proteins - genetics
ral GTP-Binding Proteins - metabolism
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1801050115