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Fat Screen Delivers Plant-derived Chemical With Antidiabetic Effects

otential cancer risks, the researchers said. Therefore, alternative approaches to treating insulin resistance are needed.

The researchers speculated that other small molecules that promote fat tissue by distinct mechanisms could be candidates for novel insulin sensitizers. By running a technologically advanced screen of more than 500 bioactive compounds, the researchers found that harmine has such a positive effect on fat. The fat cells under examination were manipulated such that they literally lit up when fat-boosting PPAR became active.

Further study of harmine's effects in diabetic mice found that the chemical increases insulin sensitivity in a manner similar to, though more roundabout than, the predominant antidiabetes drugs. Rather than triggering PPAR directly, the chemical blocks a pathway that normally inhibits fat cells' production. "Harmine inhibits an inhibitor for a net positive effect on fat" that ultimately appears to restore insulin response without some of the side effects attributed to TZDs, Tontonoz said.

The findings provide "a second example of a small molecule that both promotes fat cell differentiation in vitro and improves glucose tolerance in vivo," Tontonoz's team concluded. The biological activities of harmine and TZDs underscore the fact that links between fat tissue and insulin resistance are complex and are likely to involve not only changes in fat tissue differentiation and cell number but also changes in the fat cells' function, they said.


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