| First Author | Liu J | Year | 2016 |
| Journal | Cell | Volume | 167 |
| Issue | 4 | Pages | 1052-1066.e18 |
| PubMed ID | 27814504 | Mgi Jnum | J:238078 |
| Mgi Id | MGI:5818083 | Doi | 10.1016/j.cell.2016.10.015 |
| Citation | Liu J, et al. (2016) Inflammation Improves Glucose Homeostasis through IKKbeta-XBP1s Interaction. Cell 167(4):1052-1066.e18 |
| abstractText | It is widely believed that inflammation associated with obesity has an important role in the development of type 2 diabetes. IkappaB kinase beta (IKKbeta) is a crucial kinase that responds to inflammatory stimuli such as tumor necrosis factor alpha (TNF-alpha) 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 IKKbeta-mediated inflammation is a positive regulator of hepatic glucose homeostasis. IKKbeta 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 IKKbeta 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 IKKbeta-mediated hepatic inflammation in glucose homeostasis. |
