Role of endoplasmic reticulum stress and c-Jun NH2-terminal kinase pathways in inflammation and origin of obesity and diabetes

Diabetes. 2005 Dec;54 Suppl 2:S73-8. doi: 10.2337/diabetes.54.suppl_2.s73.

Abstract

Metabolic and immune systems are the most fundamental requirements for survival, and many metabolic and immune response pathways or nutrient- and pathogen-sensing systems have been evolutionarily highly conserved. Consequently, metabolic and immune pathways are also highly integrated and interdependent. In the past decade, it became apparent that this interface plays a critical role in the pathogenesis of chronic metabolic diseases, particularly obesity and type 2 diabetes. Importantly, the inflammatory component in obesity and diabetes is now firmly established with the discovery of causal links between inflammatory mediators, such as tumor necrosis factor (TNF)-alpha and insulin receptor signaling and the elucidation of the underlying molecular mechanisms, such as c-Jun NH2-terminal kinase (JNK)- and inhibitor of nuclear factor-kappaB kinase-mediated transcriptional and posttranslational modifications that inhibit insulin action. More recently, obesity-induced endoplasmic reticulum stress has been demonstrated to underlie the initiation of obesity-induced JNK activation, inflammatory responses, and generation of peripheral insulin resistance. This article will review the link between stress, inflammation, and metabolic disease, particularly type 2 diabetes, and discuss the mechanistic and therapeutic opportunities that emerge from this platform by focusing on JNK and endoplasmic reticulum stress responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetes Mellitus / physiopathology*
  • Endoplasmic Reticulum / enzymology
  • Endoplasmic Reticulum / physiology*
  • Humans
  • Inflammation / physiopathology*
  • Insulin / metabolism
  • Insulin Secretion
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Models, Biological
  • Obesity / physiopathology*
  • Stress, Physiological

Substances

  • Insulin
  • JNK Mitogen-Activated Protein Kinases