April 4, 2012
Study Reveals Why Rapamycin Causes Diabetes-like Symptoms
Rapamycin is an immunosuppressant derived from bacteria found on Easter Island. It was approved for organ transplant patients by the FDA in 1999. The drug helps to prevent organ rejection and is currently undergoing clinical trials as a cancer treatment. It shows promise for its anti-cancer activity and may even slow the aging process.
Pere Puigserver of Dana-Farber Cancer Institute says, “This is a drug that is pretty well known for its benefits. Rapamycin is one of the few drugs, maybe the only one, that extends lifespan in organisms from yeast to mice to primates.”As wonderful as rapamycin is, it causes diabetes-like symptoms in 15 percent of patients taking the drug. The drug causes patients to develop insulin resistance and glucose intolerance, but scientists have been baffled as to why until now.
In a new study published in Cell Metabolism, researchers report that normal mice given rapamycin were more likely to develop insulin resistance, because of a drop in insulin signaling. The insulin signaling was in turn triggered by a protein called Yin Yang 1 (YY1). YY1 was targeted by breeding mice who lacked the protein in their muscles. When they were given rapamycin they did not develop the insulin resistance.
Rapamycin works by suppressing the mTOR (mammalian target of rapamycin) signaling pathway in cells. This important signaling pathway is critical for regulating growth, proliferation, survival and motility of cells. When mTOR is elevated it is a possible signal that one has cancer.
Researchers do not know why only a small number of patients develop the diabetes-like symptoms. Further studies are continuing as to why, but they suspect that dietary factors may be the culprit.
According to Puigserver, “The possibility of increased diabetes risk needs to be taken into account in further research on the anti-aging properties of rapamycin and related compounds.”
In order to combat the insulin resistance caused by the drug, some patients may have to take anti-diabetic drugs, reports Puigserver. The additional side effects will have to be taken into account for any cost-benefit analysis of further uses of the drug including for anti-aging.