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 …

D Wei, J Li, M Shen, W Jia, N Chen, T Chen, D Su… - Diabetes, 2010 - Am Diabetes Assoc
D Wei, J Li, M Shen, W Jia, N Chen, T Chen, D Su, H Tian, S Zheng, Y Dai, A Zhao
Diabetes, 2010Am Diabetes Assoc
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 …
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 E2 (PGE2), 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 (ERK1/2) 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.
Am Diabetes Assoc