Interleukin 1β (IL-1β)-induced β cell cytotoxicity has been implicated in the autoimmune cytotoxicity of insulin-dependent diabetes mellitus. These cytotoxic effects may be mediated by nitric oxide (NO). Since long-chain fatty acids (FFA), like IL-1β, upregulate inducible nitric oxide synthase and enhance NO generation in islets, it seemed possible that islets might be protected from IL-1β-induced damage by lowering their lipid content. We found that IL-1β-induced NO production varied directly and islet cell viability inversely with islet triglyceride (TG) content. Fat-laden islets of obese rats were most vulnerable to IL-1β, while moderately fat- depleted islets of food-restricted normal rats were less vulnerable than those of free-feeding normal rats. Severely lipopenic islets of rats made chronically hyperleptinemic by adenoviral leptin gene transfer resisted IL- 1β cytotoxicity even at 300 pg/ml, the maximal concentration. Troglitazone lowered islet TG in cultured islets from both normal rats and obese, leptin- resistant rats and reduced NO production and enhanced cell survival. We conclude that measures that lower islet TG content protect against IL-1β- induced NO production and cytotoxicity. Leptin or troglitazone could provide in vivo protection against insulin-dependent diabetes mellitus.
|Original language||English (US)|
|Number of pages||5|
|Journal||Journal of Clinical Investigation|
|Publication status||Published - Oct 1 1997|
- Interleukin 1β
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