IRS2 and Insulin resistance: It gives the impressions that overexpression of miR-135 could be involved in insulin resistance, and it could affect related pathways responding normally to insulin using signaling molecules involved in removing glucose in tissues, through down-regulation of Insr. Consistent with our finding, Agarwal et al. (36) found that miR-135 level was elevated in diabetic skeletal muscle and miR-135 silence in vivo improved glucose tolerance via downregulation of IRS2, the other member of insulin signaling cascade.