Beneficial Effects of Sodium Glucose Cotransporter 2 Inhibition by Canagliflozin Independent of its Glucose Lowering Effects in Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a complex disease where hyperglycemia occurs as a result of the development of insulin resistance. It is often associated with obesity and is characterized by hyperglycemia, hyperinsulinemia, as well as hyperleptinemia. In addition to the problems associated with poor glucose control, T2DM is accompanied by a chronic inflammatory state, leading to a number of associated complications, including renal and cardiovascular injury. The sodium glucose cotransporter 2 (SGLT2) is mainly expressed in renal proximal tubules and is responsible for most of the glucose reabsorption by the tubules. Clinical trials of SGLT2 inhibitors including canagliflozin (CANA) have reported that SGLT2 inhibition lowers systolic blood pressure and attenuates body weight gain in patients with T2DM. However, the mechanisms underlying the beneficial effects of CANA have not been clearly elucidated. This study tested the effects of CANA in a T2DM mouse model which can be used for further studies to inv...