The immunosuppressant drug rapamycin, which is used in posttransplant and cancer therapies, can cause diabetes-like symptoms and insulin resistance. Now researchers in the United States and Switzerland have discovered that it does so by turning off insulin signaling in muscle, thereby preventing muscle cells from taking in blood glucose (Blättler SM et al. Cell Metab. 2012;15:505-517).
A transcription factor in muscle known as Yin Yang 1 (YY1) seems to play a key role. Rapamycin physically alters YY1 and causes it to bind to sequences that control the expression of certain genes, ultimately leading to decreased insulin signaling. Mice lacking YY1 did not develop diabetes when given rapamycin.
Hampton T. Drug Linked With Diabetes. JAMA. 2012;307(21):2247. doi:10.1001/jama.2012.5729