Inflammation and endoplasmic reticulum stress in obesity and diabetes.
Obesity is associated with chronic low-grade inflammation. Inflammatory signals interfere with insulin action and disrupt metabolic homeostasis. The c-Jun N-terminal kinase (JNK) has been identified as a central mediator of insulin resistance. Recent studies showed that in obesity compromising endoplasmic reticulum (ER) function results in insulin resistance and type 2 diabetes that are dependent on JNK activation. In contrast, enhancing ER function in transgenic mice or by the use of chemical chaperones protects against diet-induced insulin resistance. Hence, ER stress and the related signaling networks present a critical mechanism underlying obesity-induced JNK activity, inflammatory response and insulin resistance.
Hotamisligil
G S
GS
Department of Genetics and Complex Diseases, School of Public Health, Harvard University, Boston, MA, USA. ghotamis@hsph.harvard.edu
D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009765:Obesity / Q000503:physiopathology*; D017510:Protein Folding; D013312:Stress, Physiological
D048031:JNK Mitogen-Activated Protein Kinases