التفاصيل البيبلوغرافية
| العنوان: |
Cellular Production of n-3 PUFAs and Reduction of n-6-to-n-3 Ratios in the Pancreatic β-Cells and Islets Enhance Insulin Secretion and Confer Protection Against Cytokine-Induced Cell Death. |
| المؤلفون: |
Dong Wei, Li, Jie, Shen, Miaoda, Wei Jia, Nuoqi Chen, Tao Chen, Dongming Su, Haoming Tian, Shusen Zheng, Yifan Dai, Zhao, Allan |
| المصدر: |
Diabetes; Feb2010, Vol. 59 Issue 2, p471-478, 8p, 1 Diagram, 1 Chart, 4 Graphs |
| مصطلحات موضوعية: |
UNSATURATED fatty acids, PANCREATIC beta cells, ISLANDS of Langerhans, INSULIN, CYTOKINES, APOPTOSIS, TRANSGENIC mice, DIABETES |
| مستخلص: |
OBJECTIVE--To evaluate the direct impact of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the functions and viability of pancreatic β-cells. RESEARCH DESIGN AND METHODS--We developed an mfat-1 transgenic mouse model in which endogenous production of n-3 PUFAs was achieved through overexpressing a C. elegans n-3 fatty acid desaturase gene, mfat-1. The islets and INS-1 cells expressing mfat-1 were analyzed for insulin secretion and viability in response to cytokine treatment. RESULTS--The transgenic islets contained much higher levels of n-3 PUFAs and lower levels of n-6 PUFAs than the wild type. Insulin secretion stimulated by glucose, amino acids, and glucagon-like peptide-1 (GLP-1) was significantly elevated in the transgenic islets. When challenged with tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and γ-interferon (IFN-γ), the transgenic islets completely resisted cytokine-induced cell death. Adenoviral transduction of mfat-1 gene in wild-type islets and in INS-1 cells led to acute changes in the cellular levels of n-3- and n-6 PUFAs and recapitulated the results in the transgenic islets. The expression of mfat-1 led to decreased production of prostaglandin E[sub 2] (PGE[sub 2]), which in turn contributed to the elevation of insulin secretion. We further found that cytokine-induced activation of NF-κB and extracellular signal-related kinase 1/2 (ERK[sub 1/2]) was significantly attenuated and that the expression of pancreatic duodenal hemeobox-1 (PDX-1), glucokinase, and insulin-1 was increased as a result of n-3 PUFA production. CONCLUSIONS--Stable cellular production of n-3 PUFAs via mfat-1 can enhance insulin secretion and confers strong resistance to cytokine-induced β-cell destruction. The utility of mfat-1 gene in deterring type 1 diabetes should be further explored in vivo. Diabetes 59:471-478, 2010 [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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