Figure 4. TZDs ameliorate insulin resistance and diabetes by both adiponectin-dependent and -independent pathways.

We propose that there are 2 different pathways in the amelioration of insulin resistance induced by the PPARγ agonists TZDs, such as pioglitazone and probably rosiglitazone. One involves an adiponectin-dependent pathway and the other an adiponectin-independent pathway. TZDs increase adiponectin levels, ameliorating insulin resistance, increasing AMPK activation, and decreasing gluconeogenesis in the liver. On the other hand, independently of adiponectin, TZDs decrease adipocyte size, serum FFA levels, and expression of TNF-α and resistin, thus contributing to amelioration of insulin resistance in skeletal muscle.