The Selective SGLT2 Inhibitor Ipragliflozin Has a Therapeutic Effect on Nonalcoholic Steatohepatitis in MiceReport as inadecuate




The Selective SGLT2 Inhibitor Ipragliflozin Has a Therapeutic Effect on Nonalcoholic Steatohepatitis in Mice - Download this document for free, or read online. Document in PDF available to download.

Background and Aims

In recent years, nonalcoholic steatohepatitis NASH has become a considerable healthcare burden worldwide. Pathogenesis of NASH is associated with type 2 diabetes mellitus T2DM and insulin resistance. However, a specific drug to treat NASH is lacking. We investigated the effect of the selective sodium glucose cotransporter 2 inhibitor SGLT2I ipragliflozin on NASH in mice.

Methods

We used the Amylin liver NASH model AMLN, which is a diet-induced model of NASH that results in obesity and T2DM. AMLN mice were fed an AMLN diet for 20 weeks. SGLT2I mice were fed an AMLN diet for 12 weeks and an AMLN diet with 40 mg ipragliflozin-kg for 8 weeks.

Results

AMLN mice showed steatosis, inflammation, and fibrosis in the liver as well as obesity and insulin resistance, features that are recognized in human NASH. Ipragliflozin improved insulin resistance and liver injury. Ipragliflozin decreased serum levels of free fatty acids, hepatic lipid content, the number of apoptotic cells, and areas of fibrosis; it also increased lipid outflow from the liver.

Conclusions

Ipragliflozin improved the pathogenesis of NASH by reducing insulin resistance and lipotoxicity in NASH-model mice. Our results suggest that ipragliflozin has a therapeutic effect on NASH with T2DM.



Author: Yasushi Honda, Kento Imajo, Takayuki Kato, Takaomi Kessoku, Yuji Ogawa, Wataru Tomeno, Shingo Kato, Hironori Mawatari, Koji Fujit

Source: http://plos.srce.hr/



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