Sodium glucose cotransporter-2-inhibitor dapagliflozin improves nonalcoholic fatty liver disease by ameliorating dipeptidyl-peptidase-4 protein expression in diabetic mice

钠葡萄糖协同转运蛋白-2 抑制剂达格列净通过改善糖尿病小鼠的二肽基肽酶-4 蛋白表达来改善非酒精性脂肪性肝病

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作者:Dong-Ming Zhao, Cheng-Qiang Li, Yu-Man Sun, Jin-Yang Fan, Nan Wu, Ya-Nan Sun, Xin-Yi Sun

Conclusion

Dapagliflozin may be an effective drug for the treatment of T2DM-induced NAFLD and NAFLD, providing a reliable laboratory basis and new treatment methods for the clinical treatment of NAFLD.

Material and methods

Wild-type (wt) and diabetic (db/db) mouse NAFLD-induced models were used to investigate the hepatoprotective effects and potential mechanisms of dapagliflozin (a new oral hypoglycaemic drug) on type 2 diabetes mellitus (T2DM) complicated with NAFLD, and to establish wt and db/db mouse NAFLD-induced and dapagliflozin treatment models.

Methods

Wild-type (wt) and diabetic (db/db) mouse NAFLD-induced models were used to investigate the hepatoprotective effects and potential mechanisms of dapagliflozin (a new oral hypoglycaemic drug) on type 2 diabetes mellitus (T2DM) complicated with NAFLD, and to establish wt and db/db mouse NAFLD-induced and dapagliflozin treatment models.

Results

Dapagliflozin reduces blood glucose, glycosylated haemoglobin, blood lipids, and serum transaminase levels in db/db mice and improves T2DM-related liver injury accompanied by NAFLD; the mechanism may be related to the decrease in dipeptidyl-peptidase-4 (DPP4) protein expression and improvement in liver enzymes. Further mechanism-related studies by our team revealed that dapagliflozin can also downregulate the expression of DPP4 proteins in the liver and reduce serum soluble DPP4 enzyme levels, thereby improving the hepatic steatosis and insulin resistance of NAFLD.

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