학술논문

RalA controls glucose homeostasis by regulating glucose uptake in brown fat
Document Type
article
Source
Proceedings of the National Academy of Sciences of the United States of America. 115(30)
Subject
Biochemistry and Cell Biology
Biological Sciences
Diabetes
Nutrition
Obesity
1.1 Normal biological development and functioning
Underpinning research
Metabolic and endocrine
3T3-L1 Cells
Adipose Tissue
Brown
Animals
GTPase-Activating Proteins
Gene Deletion
Glucose
Glucose Transporter Type 4
Homeostasis
Mice
Mice
Knockout
ral GTP-Binding Proteins
RaIGAP
GTPase
Ral inhibitors
Glut4
insulin
RalGAP
Language
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.