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

doi:10.1073/pnas.1801050115

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 journal › Article › peer-review

36 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 language	English (US)
Pages (from-to)	7819-7824
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	115
Issue number	30
DOIs	https://doi.org/10.1073/pnas.1801050115
State	Published - Jul 24 2018
Externally published	Yes

Keywords

GTPase
Glut4
Ral inhibitors
RalGAP
insulin

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.1801050115

Cite this

Skorobogatko, Y., Dragan, M., Cordon, C., Reilly, S. M., Hung, C. W., Xia, W., Zhao, P., Wallace, M., Lackey, D. E., Chen, X. W., Osborn, O., Bogner-Strauss, J. G., Theodorescu, D., Metallo, C. M., Olefsky, J. M., & Saltiel, A. R. (2018). RalA controls glucose homeostasis by regulating glucose uptake in brown fat. Proceedings of the National Academy of Sciences of the United States of America, 115(30), 7819-7824. https://doi.org/10.1073/pnas.1801050115

Skorobogatko, Y, Dragan, M, Cordon, C, Reilly, SM, Hung, CW, Xia, W, Zhao, P, Wallace, M, Lackey, DE, Chen, XW, Osborn, O, Bogner-Strauss, JG, Theodorescu, D, Metallo, CM, Olefsky, JM & Saltiel, AR 2018, 'RalA controls glucose homeostasis by regulating glucose uptake in brown fat', Proceedings of the National Academy of Sciences of the United States of America, vol. 115, no. 30, pp. 7819-7824. https://doi.org/10.1073/pnas.1801050115

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title = "RalA controls glucose homeostasis by regulating glucose uptake in brown fat",

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.",

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AU - Skorobogatko, Yuliya

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AU - Cordon, Claudia

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AU - Hung, Chao Wei

AU - Xia, Wenmin

AU - Zhao, Peng

AU - Wallace, Martina

AU - Lackey, Denise E.

AU - Chen, Xiao Wei

AU - Osborn, Olivia

AU - Bogner-Strauss, Juliane G.

AU - Theodorescu, Dan

AU - Metallo, Christian M.

AU - Olefsky, Jerrold M.

AU - Saltiel, Alan R.

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AB - 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.

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KW - Ral inhibitors

KW - RalGAP

KW - insulin

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RalA controls glucose homeostasis by regulating glucose uptake in brown fat

Abstract

Keywords

ASJC Scopus subject areas

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