Rapamycin causes upregulation of autophagy and impairs islets function both in vitro and in vivo.

作者: M. Tanemura , Y. Ohmura , T. Deguchi , T. Machida , R. Tsukamoto

DOI: 10.1111/J.1600-6143.2011.03771.X

关键词:

摘要: Autophagy is a lysosomal degradation process of redundant or faulty cell components in normal cells. However, certain diseases are associated with dysfunctional autophagy. Rapamycin, major immunosuppressant used islet transplantation, an inhibitor mammalian target rapamycin and known to cause induction The objective this study was evaluate the in vitro and in vivo effects on pancreatic β Rapamycin induced upregulation autophagy both cultured isolated islets cells green fluorescent protein–microtubule-associated protein 1 light chain 3 transgenic mice. reduced the viability down-regulated their insulin function, both in vivo. In addition, increased percentages apoptotic dead and in vivo intact islets. Treatment 3-methyladenine, autophagy, abrogated effects restored β-cell function vitro experiments animal experiments. We conclude that rapamycin-induced dysfunction mediated through downregulation production apoptosis results also showed use these promoted survival. findings suggest targeting pathway could be beneficial promoting graft survival after transplantation.

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