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Inflammation Improves Glucose Homeostasis through IKKβ-XBP1s Interaction
Junli Liu1, Dorina Ibi1, Koji Taniguchi2
1Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02130, USA.
Cell
|November 5, 2016
Summary
Inflammation involving IκB kinase beta (IKKβ) positively regulates liver glucose balance. Enhancing IKKβ in obese mice improved insulin sensitivity and glucose homeostasis by reducing ER stress.
Area of Science:
- Metabolism and Endocrinology
- Molecular Biology
- Cellular Signaling
Background:
- Obesity-associated inflammation is linked to type 2 diabetes development.
- IκB kinase beta (IKKβ) is a key kinase in inflammatory pathways, often implicated in insulin resistance.
- The precise role of IKKβ-mediated inflammation in hepatic glucose metabolism is not fully understood.
Purpose of the Study:
- To investigate the role of IKKβ-mediated inflammation in hepatic glucose homeostasis.
- To determine if modulating IKKβ activity impacts insulin sensitivity and glucose regulation in obesity.
Main Methods:
- Utilized three distinct experimental strategies to elevate IKKβ activity specifically in the liver of obese mice.
- Assessed the impact of enhanced IKKβ activity on X-Box Binding Protein 1 splicing (XBP1s) activity.
- Monitored endoplasmic reticulum (ER) stress levels and evaluated insulin sensitivity and glucose homeostasis.
Main Results:
- Increased IKKβ activity led to enhanced XBP1s activity in the liver.
- Elevated IKKβ activity resulted in reduced ER stress.
- Obese mice with enhanced hepatic IKKβ activity showed significant improvements in insulin sensitivity and glucose homeostasis.
Conclusions:
- Contrary to prevailing beliefs, IKKβ-mediated hepatic inflammation acts as a positive regulator of glucose homeostasis.
- IKKβ phosphorylation of XBP1s is a key mechanism driving these beneficial effects.
- Targeting hepatic IKKβ activity may offer a novel therapeutic strategy for managing insulin resistance and type 2 diabetes.
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