For the past two decades, a great deal of research has been published concerning adiponectin (APN), an abundant protein responsible for regulating numerous biologic functions including antioxidative, antinitrative, anti-inflammatory, and cardioprotective effects. A review of APN and its two major receptors is timely because of new findings concerning the mechanisms by which APN signaling may be altered in pathologic processes such as diabetes and heart failure. In this review we elaborate on currently known information regarding the physiologic role of APN and the known mechanisms underlying pathologic APN resistance - namely, APN receptor downregulation and phosphorylation - and provide insight regarding the future directions of APN research including an assessment of the clinical applicability of preventing pathologic post-translational modification of the APN receptor.
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