Adiponectin is a fat-derived hormone that seems to have a crucial role in the protection from insulin resistance/diabetes and atherosclerosis. This study identifies an orally active compound, obtained by screening small molecules in the chemical library at the University of Tokyo's Open Innovation Center for Drug Discovery, that binds to and activates the AdipoR1 and AdipoR2 receptors that mediate adiponectin's antidiabetic action. Named AdipRon, the compound ameliorates insulin resistance and glucose intolerance in mice on a high-fat diet and in genetically obese mice. AdipoRon also extends the shortened lifespan of db/db mice on a high-fat diet. If this work can be extrapolated to humans, orally active agonists such as AdipoRon could offer a promising new approach to treat obesity-related diseases such as type 2 diabetes.
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