|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5695
|
|
pubmed:dateCreated |
2004-10-15
|
|
pubmed:abstractText |
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.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ern2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ern2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Irs1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Irs1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PERK kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tunicamycin,
http://linkedlifedata.com/resource/pubmed/chemical/eIF-2 Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/regulatory factor X transcription...
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Oct
|
|
pubmed:issn |
1095-9203
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
15
|
|
pubmed:volume |
306
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
457-61
|
|
pubmed:dateRevised |
2011-11-17
|
|
pubmed:meshHeading |
pubmed-meshheading:15486293-Adipose Tissue,
pubmed-meshheading:15486293-Animals,
pubmed-meshheading:15486293-Cells, Cultured,
pubmed-meshheading:15486293-DNA-Binding Proteins,
pubmed-meshheading:15486293-Diabetes Mellitus, Type 2,
pubmed-meshheading:15486293-Endoplasmic Reticulum,
pubmed-meshheading:15486293-Glucose,
pubmed-meshheading:15486293-Homeostasis,
pubmed-meshheading:15486293-Insulin,
pubmed-meshheading:15486293-Insulin Receptor Substrate Proteins,
pubmed-meshheading:15486293-Insulin Resistance,
pubmed-meshheading:15486293-Liver,
pubmed-meshheading:15486293-Membrane Proteins,
pubmed-meshheading:15486293-Mice,
pubmed-meshheading:15486293-Mice, Inbred BALB C,
pubmed-meshheading:15486293-Mice, Obese,
pubmed-meshheading:15486293-Mitogen-Activated Protein Kinase 8,
pubmed-meshheading:15486293-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15486293-Muscle, Skeletal,
pubmed-meshheading:15486293-Mutation,
pubmed-meshheading:15486293-Nuclear Proteins,
pubmed-meshheading:15486293-Obesity,
pubmed-meshheading:15486293-Phosphoproteins,
pubmed-meshheading:15486293-Phosphorylation,
pubmed-meshheading:15486293-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15486293-Rats,
pubmed-meshheading:15486293-Receptor, Insulin,
pubmed-meshheading:15486293-Signal Transduction,
pubmed-meshheading:15486293-Transcription Factors,
pubmed-meshheading:15486293-Tunicamycin,
pubmed-meshheading:15486293-eIF-2 Kinase
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes.
|
|
pubmed:affiliation |
Department of Genetics and Complex Diseases, Harvard Medical School, Boston, MA 02115, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
