RalA controls glucose homeostasis by regulating glucose uptake in brown fat

Y Skorobogatko, M Dragan, C Cordon… - Proceedings of the …, 2018 - National Acad Sciences
Y Skorobogatko, M Dragan, C Cordon, SM Reilly, CW Hung, W Xia, P Zhao, M Wallace
Proceedings of the National Academy of Sciences, 2018National Acad Sciences
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 …
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.
National Acad Sciences