April 10, 2012

The Yin and the yang of a drug causing diabetes symptoms and anti-aging effects

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Rapamycin, brand name Rapamune, is an immune-suppressant drug that also has shown anti-cancer activity and may even slow ageing.

About 15% of patients who take rapamycin develop insulin resistance and glucose intolerance. A recent study published in Cell Metabolism may explain why the drug has negative effects of glucose metabolism.

In the study, normal mice given  rapamycin were more likely to have trouble regulating their blood sugar because of a drop in insulin signaling. The decreased insulin signaling was triggered by activity of a protein called Yin Yang 1, or YY1. Mice that were bred without the YY1 gene were immune to the diabetic effects of rapamycin

Rapamycin is an mTOR inhibitor. mTOR inhibitors have been identified as potential anticancer agents in various cancers. In fact, Novartis has a site Target mTOR to educate on the role mTOR plays in the development of  some tumors.

The anti-aging effects of the drug are tricky. By inhibiting mTOR you are also inhibiting the growth of pancreatic beta cells. This results in  caloric restriction. An article arguing the ability of rapamycin to slow aging in mice does not warrant increasing the risk of  diabetes. The appeal of a drug that may offer anti-aging effects should be cautiously considered.

For what it’s worth – I can add a personal note on the use of Rapamune. When I had my kidney transplant in May 2010 I tried different combinations of anti-rejection drugs. Rapamune was one I tried. It did cause insulin resistance. It also caused hives. I guess I’m a statistic.

Further infestation for the clinical importance of rapamycin is significant for the treatment of age-related human diseases and lifespan longevity.  How can we get Yin Yang 1 to play well with others?

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