RaIA 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 RaIA by insulin, via inhibition of its GTPase activating complex RaIGAP. Here, we evaluate the role of RaIA in glucose uptake in vivo with specific chemical inhibitors and by generation of mice with adipocyte-specific knockout of RaIGAPB. RaIA was profoundly activated in brown adipose tissue after feeding, and its inhibition prevented Glut4 exocytosis. RaIGAPB knockout mice with diet-induced obesity were protected from the development of metabolic disease due to increased glucose uptake into brown fat. Thus, RaIA plays a crucial role in glucose transport in adipose tissue in vivo.