Structure and function analysis of adiponectin receptors toward development of novel antidiabetic agents promoting healthy longevity

Abstract

Plasma adiponectin levels and expression of its receptors, AdipoRs are decreased in obesity, which cause insulin resistance and diabetes. AdipoR-deficient mice exhibit insulin resistance and impaired glucose tolerance. Moreover, newly identified AdipoR agonists not only improve insulin resistance but prolong lifespan shortened by obesity via AdipoR. Furthermore, efforts to promote structure-based drug discovery research at our laboratory have led to the first ever successful crystallization of AdipoR as well as to clarification of their structures. Structural analysis of AdipoRs as key molecules in lifestyle-related diseases is thus expected to lead not only to the acceleration of structure-based drug discovery but to the elucidation of novel aspects of the AdipoR structures and functions in the years to come. Finally, with the development of novel AdipoR-targeted antidiabetic agents also capable of prolonging lifespan, the attainment of healthy longevity may finally be brought within reach.