Increased CD36 protein as a response to defective insulin signaling in macrophages
| Autor: | Chien-Ping Liang, Ira Tabas, Ronald Carnemolla, Haruka Okamoto, Domenico Accili, Alan R. Tall, Seongah Han |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
CD36 Antigens
Time Factors Transcription Genetic medicine.medical_treatment CD36 Mice Obese Receptors Cytoplasmic and Nuclear Mice Phosphatidylinositol 3-Kinases Insulin Enzyme Inhibitors Phosphorylation Receptor Foam cell Reverse Transcriptase Polymerase Chain Reaction General Medicine Glutathione Lipoproteins LDL Electrophoresis Polyacrylamide Gel Signal transduction Rosiglitazone Protein Binding Signal Transduction medicine.drug medicine.medical_specialty Morpholines Blotting Western Biology Article Insulin resistance Internal medicine medicine Animals Hypoglycemic Agents Macrophages Blotting Northern medicine.disease Mice Inbred C57BL Oxygen Insulin receptor Endocrinology Chromones biology.protein Tyrosine Thiazolidinediones Insulin Resistance Foam Cells Transcription Factors |
| Zdroj: | Journal of Clinical Investigation. 113:764-773 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci19528 |
| Popis: | Accelerated atherosclerosis is a major cause of morbidity and death in insulin-resistant states such as obesity and the metabolic syndrome, but the underlying mechanisms are poorly understood. We show that macrophages from obese (ob/ob) mice have increased binding and uptake of oxidized LDL, in part due to a post-transcriptional increase in CD36 protein. Macrophages from ob/ob mice are also insulin resistant, as shown by reduced expression and signaling of insulin receptors. Three lines of evidence indicate that the increase in CD36 is caused by defective insulin signaling: (a) Treatment of wild-type macrophages with LY294002, an inhibitor of insulin signaling via PI3K, results in an increase in CD36; (b) insulin receptor knockout macrophages show a post-transcriptional increase in CD36 protein; and (c) administration of thiazolidinediones to intact ob/ob mice and ob/ob, LDL receptor-deficient mice results in a reversal of macrophage insulin receptor defects and decreases CD36 protein. The last finding contrasts with the increase in CD36 that results from treatment of macrophages with these drugs ex vivo. The results suggest that defective macrophage insulin signaling predisposes to foam cell formation and atherosclerosis in insulin-resistant states and that this is reversed in vivo by treatment with PPAR-gamma activators. |
| Databáze: | OpenAIRE |
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