INS and Insulin resistance: Finally, recent evidence indicates that the detrimental effects of aldosterone excess on insulin signaling are mediated by inflammatory/oxidative stress mechanisms of mineralocorticoids.159 To support the involvement of the aldosterone stress mechanism in the TG(mRen2)22 rat, which has insulin resistance,160in vivo MR antagonism with spironolactone substantially improves ex vivo insulin-stimulated increases in glucose uptake in skeletal muscle.