Lamming and Uncoupled from Longevity Rapamycin - Induced Insulin Resistance Is Mediated by mTORC 2 Loss
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منابع مشابه
Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity.
Rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1), extends the life spans of yeast, flies, and mice. Calorie restriction, which increases life span and insulin sensitivity, is proposed to function by inhibition of mTORC1, yet paradoxically, chronic administration of rapamycin substantially impairs glucose tolerance and insulin action. We demonstrate that rapamycin di...
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Rapamycin, a FDA-approved pharmaceutical, has received significant attention as a possible anti-aging agent since the groundbreaking discovery in 2009 that rapamycin treatment significantly extends the lifespan of mice [1]. Excitingly, rapamycin not only extends lifespan, it also extends healthspan in rodent models, preventing and delaying the onset of age-related diseases, including cancer and...
متن کاملYoung and old genetically heterogeneous HET3 mice on a rapamycin diet are glucose intolerant but insulin sensitive.
Rapamycin, an inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, extends the life span of yeast, worms, flies, and mice. Interventions that promote longevity are often correlated with increased insulin sensitivity, and it therefore is surprising that chronic rapamycin treatment of mice, rats, and humans is associated with insulin resistance (J Am Soc Nephrol., 19, 2008, ...
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Rapamycin, an inhibitor of mTOR complex 1 (mTORC1), improves insulin sensitivity in acute studies in vitro and in vivo by disrupting a negative feedback loop mediated by S6 kinase. We find that rapamycin has a clear biphasic effect on insulin sensitivity in C2C12 myotubes, with enhanced responsiveness during the first hour that declines to almost complete insulin resistance by 24-48 h. We and o...
متن کاملTOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO.
The TOR kinase, which is present in the functionally distinct complexes TORC1 and TORC2, is essential for growth but associated with disease and aging. Elucidation of how TOR influences life span will identify mechanisms of fundamental importance in aging and TOR functions. Here we show that when TORC1 is inhibited genetically in C. elegans, SKN-1/Nrf, and DAF-16/FoxO activate protective genes,...
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