The sodiumglucose cotransporter 2 inhibitor luseogliflozin can suppress muscle atrophy in Db/Db mice by suppressing the expression of foxo1

Abstract

We investigated the effect of the sodium glucose cotransporter2 inhibitor (SGLT2i) luseogliflozin on skeletal muscle. Eightweek old mice were fed a standard diet or the standard diet with added luseogliflozin for 8 weeks. The mice were divided into the following four genotype/dietary groups: Db/m mice without SGLT2i, Db/m mice with SGLT2i inhibitor, Db/Db without SGLT2i, and Db/Db with SGLT2i. Among the mice with and without SGLT2i, the ratio of soleus and plantaris muscle to body weight in the Db/Db mice was significantly lower than that in the Db/m mice. The cross sectional area of soleus muscle in the Db/Db mice without SGLT2i was significantly higher than that in the Db/Db mice with SGLT2i. The expression of foxo1 in soleus muscle of the Db/Db mice was significantly higher than that of the Db/m mice, and the foxo1 expression of the Db/Db mice with SGLT2i was significantly lower than that of the mice without SGLT2i. The fluorescence intensity of foxo1 in the Db/Db mice fed SGLT2i was significantly lower than that in the Db/Db mice without SGLT2i. The admin istration of luseogliflozin resulted in the suppression of both the increased foxo1 expression and the reduced muscle crosssectional area in the soleus muscle of Db/Db mice.