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Since its initial description in 1995 (1), few molecules in metabolism research have received as much continued interest as adiponectin. The focus of more than 12,000 publications, this adipokine has been widely studied in preclinical and clinical settings under a variety of physiological and pathophysiological conditions (2). Adiponectin is produced by adipocytes and released into circulation. It is considered protective, based on the potent insulin-sensitizing, antilipotoxic, anti-apoptotic, and anti-inflammatory actions it exerts on different cell types. These compelling effects marked adiponectin as a possible drug target for diabetes and other obesity-associated diseases. The long wait for a small-molecule agonist for adiponectin receptors may soon be over. Okada-Iwabu et al. (3) have identified a compound that is an adiponectin receptor agonist in rodent and cell culture models. It represents an important step toward filling an unmet clinical need for additional therapeutic options against diabetes, obesity, and other associated disorders.