mTORC1 Activates SREBP-1c and Uncouples Lipogenesis From Gluconeogenesis
Author(s)Sabatini, David M.; Laplante, Mathieu
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Insulin resistance, which is defined as the inability of insulin to promote efficient glucose uptake by peripheral tissues, is a metabolic condition associated with obesity, type 2 diabetes, dyslipidemia, and cardiovascular diseases. Although important advances in our understanding of the molecular mechanisms involved in the development of insulin resistance have been made during the last decades ( 1), many questions remain. One of these questions relates to the fact that, in the liver of many insulin-resistant mouse models, insulin fails to suppress glucose production (gluconeogenesis) but continues to promote lipid synthesis (lipogenesis) ( 2). This selective hepatic insulin resistance contributes to hyperglycemia and hyperlipidemia and suggests that the insulin-signaling pathway must bifurcate upstream of lipogenesis and gluconeogenesis. In this issue of PNAS, Li et al. ( 3) identify a bifurcation point in the insulin-signaling pathway that could help resolve this important paradox.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Proceedings of the National Academy of Sciences of the United States of America
National Academy of Sciences
Laplante, Mathieu, and David M. Sabatini. “mTORC1 activates SREBP-1c and uncouples lipogenesis from gluconeogenesis.” Proceedings of the National Academy of Sciences 107.8 (2010): 3281 -3282. ©2010 by the National Academy of Sciences.
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