Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes - PubMed (original) (raw)

. 2004 Oct 15;306(5695):457-61.

doi: 10.1126/science.1103160.

Affiliations

• PMID: 15486293
• DOI: 10.1126/science.1103160

Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes

Umut Ozcan et al. Science. 2004.

Abstract

Obesity contributes to the development of type 2 diabetes, but the underlying mechanisms are poorly understood. Using cell culture and mouse models, we show that obesity causes endoplasmic reticulum (ER) stress. This stress in turn leads to suppression of insulin receptor signaling through hyperactivation of c-Jun N-terminal kinase (JNK) and subsequent serine phosphorylation of insulin receptor substrate-1 (IRS-1). Mice deficient in X-box-binding protein-1 (XBP-1), a transcription factor that modulates the ER stress response, develop insulin resistance. These findings demonstrate that ER stress is a central feature of peripheral insulin resistance and type 2 diabetes at the molecular, cellular, and organismal levels. Pharmacologic manipulation of this pathway may offer novel opportunities for treating these common diseases.

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Comment in

• Biomedicine. Insulin resistance takes a trip through the ER.
  Muoio DM, Newgard CB. Muoio DM, et al. Science. 2004 Oct 15;306(5695):425-6. doi: 10.1126/science.1104680. Science. 2004. PMID: 15486283 No abstract available.

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