@article{f669560098bc4d068fd364d81f47399a,
title = "Inflammation Improves Glucose Homeostasis through IKKβ-XBP1s Interaction",
abstract = "It is widely believed that inflammation associated with obesity has an important role in the development of type 2 diabetes. IκB kinase beta (IKKβ) is a crucial kinase that responds to inflammatory stimuli such as tumor necrosis factor α (TNF-α) by initiating a variety of intracellular signaling cascades and is considered to be a key element in the inflammation-mediated development of insulin resistance. We show here, contrary to expectation, that IKKβ-mediated inflammation is a positive regulator of hepatic glucose homeostasis. IKKβ phosphorylates the spliced form of X-Box Binding Protein 1 (XBP1s) and increases the activity of XBP1s. We have used three experimental approaches to enhance the IKKβ activity in the liver of obese mice and observed increased XBP1s activity, reduced ER stress, and a significant improvement in insulin sensitivity and consequently in glucose homeostasis. Our results reveal a beneficial role of IKKβ-mediated hepatic inflammation in glucose homeostasis.",
keywords = "ER stress, IKKβ, UPR, XBP1s, diabetes, glucose metabolism, inflammation, insulin resistance, obesity, unfolded protein response",
author = "Junli Liu and Dorina Ibi and Koji Taniguchi and Jaemin Lee and Hilde Herrema and Bedia Akosman and Patrick Mucka and {Salazar Hernandez}, {Mario Andres} and Uyar, {Muhemmet Fatih} and Park, {Sang Won} and Michael Karin and Umut Ozcan",
note = "Funding Information: We thank Morris F. White and Rongya Tao for helping us to perform the hyperinsulinemic-euglycemic clamp experiments. This work was supported by funds provided to U.O. from Department of Medicine, Boston Children{\textquoteright}s Hospital, by NIH grants R01DK081009 and R01DK098496 to U.O., by the American Diabetes Association{\textquoteright}s Career Development grant #7-09-CD-10 , and by NIH grant AI043477 to M.K. U.O. is a scientific founder, shareholder, and member of the scientific advisory board and board of directors of ERX Pharmaceuticals, Inc. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = nov,
day = "3",
doi = "10.1016/j.cell.2016.10.015",
language = "English",
volume = "167",
pages = "1052--1066.e18",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}
