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Study Describes Rapamycin Diabetic-Like State Side Effect Mechanism

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Rapamycin Diabetic

Researchers have discovered what is the mechanism underlying the symptoms of diabetes in patients treated with rapamycin. Researchers at Dana-Farber Cancer Institute have found that the link between Yin Yang 1 (YY1), a transcription factor, and rapamycin. Rapamycin is an immunosuppressive drug used initially in kidney transplantation, but gradually it  has been found that it has cancer and anti-aging effects.

Rapamycin or sirolimus is actually a macrolide for the first time extracted from the bacterium Streptomyces hygroscopicus present in soil from Easter Island. Originally, rapamycin was used as antifungal, but scientists found it more useful as immunosuppressive and antiproliferative agent. As an immunosuppressant, rapamycin prevents T and B cell activation by inhibiting the response of these cells to interleukin-2. Therefore, rapamycin  was approved in 1999 by the FDA as immunosuppressive organ transplantation.

Rapamycin

Rapamycin

Regarding the anticancer properties, rapamycin inhibits mTOR signaling pathway (mTOR stands for “mammalian target of rapamycin”). mTOR is involved in regulating growth, proliferation and cell life. Moreover, mTOR is also one of the markers of cancer. Due to this property, rapamycin is being evaluated as a cancer treatment in several clinical trials. This drug is in clinical trials as a treatment for kidney cancer, brain tumors, lymphomas, etc. However, it was found that 15% of patients treated with rapamycin develop insulin resistance and glucose intolerance. So far, researchers have not found an answer to these effects, but study led by researchers at Dana-Farber Cancer Institute could elucidate the mechanism by which rapamycin induces diabetes.

Studies on rats showed that those treated with rapamycin had problems with regulating blood sugar,  the insulin resistance being caused by the activity of a protein Yin Yang 1, or YY1. Researchers have found that YY1 is the target of rapamycin as rats without this protein have not developed problems with blood sugar regulation. “”We thought that maybe YY1 was responsible for the diabetic effects,” says Puigserver PhD, senior author of the report published in Cell Metabolism.
Although study results are promising, researchers still have to investigate why only some patients develop diabetes after treatment with rapamycin.

Another property of rapamycin exploited more recently is related to extending the life of cells. In fact, many studies are focused precisely on these anti-aging. The first studies which showed that rapamycin increases lifespan in eukaryotes have been completed in 2006. Later studies in rats had positive results, that is  lifespan of rats was increased by 28-38%. However, it is unknown whether the same people might have given promising results as rapamycin suppress immunity.