Chemical found in plants may fight diabetes without side effects

Researchers have discovered that an ingredient found in some plants fights diabetes in mice without some of the side effects attributed to other anti-diabetes drugs.

Washington, May 9 : Researchers have discovered that an ingredient found in some plants fights diabetes in mice without some of the side effects attributed to other anti-diabetes drugs.

The chemical they pinpointed, known as harmine, was first isolated more than 150 years ago from plants traditionally included in ritual and medicinal preparations around the world,

The work suggests a new approach for treating insulin resistance that might complement the use of preexisting drugs and, more generally, provides validation for fat cell screens as a promising strategy for identifying new metabolic drugs, according to the researchers.

"While harmine itself has effects on the central nervous system that may preclude its use. It may eventually be possible to separate the nervous system and metabolic effects of harmine through optimization of the chemical structure," said Peter Tontonoz, a Howard Hughes Medical Institute investigator at the University of California, Los Angeles.

Harmine has been known to induce hallucinations,convulsions, and tremors. The principal class of drugs prescribed for obesity-related diabetes, called thiazolidinediones or TZDs, work through a counterintuitive mechanism: they restore insulin sensitivity by activating a central promoter of fat tissue production called peroxisome proliferator-activated receptor � (PPAR�).

"The current explanation for this paradoxical mode of action is the idea that the body needs a place to store lipids," Tontonoz said.

Despite their efficacy, the development and clinical use of TZDs is limited by adverse effects such as fluid retention, weight gain, congestive heart failure, liver toxicity, and potential cancer risks, the researchers said. Therefore, alternative approaches to treating nsulin resistance are needed.

Further study of harmine's effects in diabetic mice found that the chemical increases insulin sensitivity in a manner similar to, though ore 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," the team said.

The study is reported in the May issue of the journal Cell Metabolism, published by Cell Press.

ANI