PEDF expression is inhibited by insulin treatment in adipose tissue via suppressing 11β-HSD1
| العنوان: | PEDF expression is inhibited by insulin treatment in adipose tissue via suppressing 11β-HSD1 |
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| المؤلفون: | Hongrong Deng, Zonglan Chen, Jianping Weng, Fen Xu, Yinli Zhou, Yan Bi, Wei-ping Sun, Yi Zhao |
| المصدر: | PLoS ONE, Vol 8, Iss 12, p e84016 (2013) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, medicine.medical_treatment, Science, Adipose tissue, Inflammation, Dexamethasone, Pathogenesis, Rats, Sprague-Dawley, Mice, Insulin resistance, PEDF, Internal medicine, 3T3-L1 Cells, 11-beta-Hydroxysteroid Dehydrogenase Type 1, medicine, Animals, Humans, Insulin, Nerve Growth Factors, Eye Proteins, Serpins, Gene knockdown, Multidisciplinary, Chemistry, Tumor Necrosis Factor-alpha, NF-kappa B, Middle Aged, medicine.disease, Rats, Endocrinology, Adipose Tissue, Diabetes Mellitus, Type 2, Gene Expression Regulation, Medicine, Tumor necrosis factor alpha, Female, medicine.symptom, Insulin Resistance, Research Article |
| الوصف: | Early intensive insulin therapy improves insulin sensitivity in type 2 diabetic patients; while the underlying mechanism remains largely unknown. Pigment epithelium-derived factor (PEDF), an anti-angiogenic factor, is believed to be involved in the pathogenesis of insulin resistance. Here, we hypothesize that PEDF might be down regulated by insulin and then lead to the improved insulin resistance in type 2 diabetic patients during insulin therapy. We addressed this issue by investigating insulin regulation of PEDF expression in diabetic conditions. The results showed that serum PEDF was reduced by 15% in newly diagnosed type 2 diabetic patients after insulin therapy. In adipose tissue of diabetic Sprague-Dawley rats, PEDF expression was associated with TNF-α elevation and it could be decreased both in serum and in adipose tissue by insulin treatment. In adipocytes, PEDF was induced by TNF-α through activation of NF-κB. The response was inhibited by knockdown and enhanced by over expression of NF-κB p65. However, PEDF expression was indirectly, not directly, induced by NF-κB which promoted 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) expression in adipocytes. 11β-HSD1 is likely to stimulate PEDF expression through production of active form of glucocorticoids as dexamethasone induced PEDF expression in adipose tissue. Insulin inhibited PEDF by down-regulating 11β-HSD1 expression. The results suggest that PEDF activity is induced by inflammation and decreased by insulin through targeting 11β-HSD1/glucocorticoid pathway in adipose tissue of diabetic patients. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3f8e6d20469ade11d9b72045929dd786Test https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24367624/pdf/?tool=EBITest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3f8e6d20469ade11d9b72045929dd786 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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