This review discusses the association between adiponectin and insulin resistance. It is now well recognized that adiponectin is an insulin-sensitizing adipokine. In fact, studies on adiponectin knockout mice models reported that they were more insulin resistant than controls. Moreover, administration of recombinant full length monomeric adiponectin was shown to enhance whole body insulin sensitivity in mice. No similar direct evidence is available in humans. However, large-scale genome-wide association study of circulating adiponectin levels has recently revealed a novel variant in the ARL15 gene which appears to be associated with lower serum adiponectin levels. The ARL15 protein has been reported to be involved in insulin signalling and insulin-stimulated glucose transport, its expression is observed in skeletal muscle and was also associated with an increased risk of type 2 diabetes. On the other hand, no proof exists that adiponectin modulates insulin resistance in humans, and various evidence suggest that low adiponectin levels could be a consequence of insulin resistance. Furthermore, direct testing of the effect of insulin infusion in healthy subjects has shown that insulin suppresses adiponectin levels in vivo. Therefore, some consistent evidence suggest that adiponectin acts systemically to improve insulin sensitivity in mice, and also that it is suppressed by hyperinsulinemia in prevalent forms of insulin resistance in both humans and mice. The relationship between adiponectin and insulin action in humans is therefore very complex. Additional studies are needed to better understand the regulation of adiponectin and its physiological roles in order to use it as a new therapeutic target.
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