Science (American Association for the Advancement of Science), 2006-08, Vol.313 (5790), p.1137-1140
2006
Details
- Autor(en) / Beteiligte
- Titel
- Chemical Chaperones Reduce ER Stress and Restore Glucose Homeostasis in a Mouse Model of Type 2 Diabetes
- Ist Teil von
- Science (American Association for the Advancement of Science), 2006-08, Vol.313 (5790), p.1137-1140
- Ort / Verlag
- Washington, DC: American Association for the Advancement of Science
- Erscheinungsjahr
- 2006
- Link zum Volltext
- Quelle
- American Association for the Advancement of Science
- Beschreibungen/Notizen
- Endoplasmic reticulum (ER) stress is a key link between obesity, insulin resistance, and type 2 diabetes. Here, we provide evidence that this mechanistic link can be exploited for therapeutic purposes with orally active chemical chaperones. 4-Phenyl butyric acid and taurine-conjugated ursodeoxycholic acid alleviated ER stress in cells and whole animals. Treatment of obese and diabetic mice with these compounds resulted in normalization of hyperglycemia, restoration of systemic insulin sensitivity, resolution of fatty liver disease, and enhancement of insulin action in liver, muscle, and adipose tissues. Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.1128294Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4741373
- Format
- –
- Schlagworte
- Adipose Tissue - metabolism, Adipose tissues, Animals, Biochemistry, Biological and medical sciences, Blood Glucose - metabolism, Cell Line, Tumor, Diabetes, Diabetes Mellitus, Type 2 - drug therapy, Diabetes Mellitus, Type 2 - metabolism, Diabetes. Impaired glucose tolerance, Disease Models, Animal, eIF-2 Kinase - metabolism, Endocrine pancreas. Apud cells (diseases), Endocrinopathies, Endoplasmic Reticulum - drug effects, Endoplasmic Reticulum - metabolism, Enzyme Activation, Etiopathogenesis. Screening. Investigations. Target tissue resistance, Eukaryotic Initiation Factor-2 - metabolism, Genetics, Glucose - administration & dosage, Glucose - metabolism, Glucose Tolerance Test, Homeostasis, Insulin, Insulin - blood, Insulin - pharmacology, Insulin Resistance, JNK Mitogen-Activated Protein Kinases - metabolism, Liver, Liver - metabolism, Medical sciences, Medical treatment, Metabolic diseases, Mice, Mice, Obese, Obesity, Phenylbutyrates - pharmacology, Phenylbutyrates - therapeutic use, Phosphorylation, Receptor, Insulin - metabolism, Receptors, Research fellowships, Rodents, Signal Transduction, Taurochenodeoxycholic Acid - pharmacology, Taurochenodeoxycholic Acid - therapeutic use, Type 2 diabetes mellitus, Vehicle performance