In the present study, we demonstrate that during the development of type 2 diabetes, RDX attenuates systemic and regional sympathetic hyperactivity, and substantially reduces glucose intolerance and insulin insensitivity through two different mechanisms, specifically: (1) improvement of glucose uptake by peripheral tissues; and (2) enhancement of urinary glucose excretion by suppression of renal Sglt2 overexpression. Here, INS is linked to type 2 diabetes mellitus.