The majority of individuals who have type 2 (insulin-resistant) diabetes are also obese, but to date the cellular mechanism by which fat cells become insulin resistant has been unknown. Now, researchers at the University of Pennsylvania suggest that a hormone—dubbed resistin—may be the missing link (Nature 409, 307–312, 2001). The researchers screened fat cells (adipocytes) for unique messenger RNAs, the expression of which was suppressed by thiazoladinediones (TZDs). (TZDs comprise a class of antidiabetic drugs that work by partially restoring insulin sensitivity of cells.) Using this novel screen, the researchers identified a unique gene product, resistin, which made adipocytes resistant to insulin. Resistin levels are elevated in obese mice, and anti-resistin antibodies and TZDs lowered their elevated glucose levels. Mitchell Lazar, senior author on the paper, says that the team is now “trying to identify the receptor [for resistin] using a candidate-gene approach, and we are also actively searching for the cellular targets of resistin.” Resistin offers an important new target for the treatment of type 2 diabetes patients.