1943-P: The Sodium-Glucose Cotransporter 2 Inhibitor Luseogliflozin Can Suppress Muscle Atrophy in Db/Db Mice by Suppressing the Expression of Foxo1

Abstract

Here we investigated the effect of the sodium glucose cotransporter-2 inhibitor (SGLT2i) luseogliflozin on skeletal muscle. Eight-week-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 (w/o) SGLT2i, Db/m mice with SGLT2i, Db/Db w/o SGLT2i, and Db/Db with SGLT2i. After the 8-week dietary treatment, we investigated the changes in body weight, glucose tolerance, and muscle in each group. Among the mice with and w/o 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 w/o 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 w/o SGLT2i. The fluorescence intensity of foxo1 in the Db/Db mice fed SGLT2i was significantly lower than that in the Db/Db mice w/o SGLT2i.The administration of luseogliflozin resulted in the suppression of both the increased foxo1 expression and the reduced muscle cross-sectional area in the soleus muscle of Db/Db mice. Disclosure R. Bamba: None. T. Kimura: None. T. Okamura: None. Y. Hashimoto: Research Support; Self; Asahi Kasei Pharma. T. Osaka: None. T. Senmaru: None. M. Fukui: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Johnson & Johnson, Kyowa Hakko Kirin Co., Ltd., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; AstraZeneca, Eli Lilly and Company, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited.