Inflammation Improves Glucose Homeostasis through IKKβ-XBP1s Interaction
| Autor: | Jaemin Lee, Dorina Ibi, Muhemmet Fatih Uyar, Mario Andrés Salazar Hernández, Hilde Herrema, Umut Ozcan, Bedia Akosman, Sang Won Park, Junli Liu, Patrick Mucka, Koji Taniguchi, Michael Karin |
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| Rok vydání: | 2016 |
| Předmět: |
Male
X-Box Binding Protein 1 0301 basic medicine obesity Mice Obese UPR IκB kinase Inbred C57BL Medical and Health Sciences Obese Oral and gastrointestinal Mice insulin resistance 2.1 Biological and endogenous factors Homeostasis Glucose homeostasis Aetiology Phosphorylation Tumor diabetes Protein Stability Kinase Liver Disease unfolded protein response Biological Sciences Endoplasmic Reticulum Stress I-kappa B Kinase Liver medicine.symptom ER stress Type 2 medicine.medical_specialty glucose metabolism IKKβ Inflammation Carbohydrate metabolism Biology Article General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences Insulin resistance Cell Line Tumor Internal medicine Diabetes Mellitus Genetics medicine Animals Humans Obesity Metabolic and endocrine Nutrition medicine.disease Mice Inbred C57BL Glucose 030104 developmental biology Endocrinology Diabetes Mellitus Type 2 inflammation Unfolded protein response XBP1s Digestive Diseases Developmental Biology |
| Zdroj: | Cell, vol 167, iss 4 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2016.10.015 |
| Popis: | 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 (TNFα), 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. |
| Databáze: | OpenAIRE |
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