Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene lead to CF, a life-threating autosomal recessive genetic disease. While recently approved Trikafta dramatically ameliorates CF lung diseases, there is still a lack of effective medicine to treat CF-associated liver disease (CFLD). To address this medical need, we used a recently established CF rabbit model to test whether sotagliflozin, a sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor drug that is approved to treat diabetes, can be repurposed to treat CFLD. Sotagliflozin treatment led to systemic benefits to CF rabbits, evidenced by increased appetite and weight gain as well as prolonged lifespan. For CF liver-related phenotypes, the animals benefited from normalized blood chemistry and bile acid parameters. Furthermore, sotagliflozin alleviated nonalcoholic steatohepatitis–like phenotypes, including liver fibrosis. Intriguingly, sotagliflozin treatment markedly reduced the otherwise elevated endoplasmic reticulum stress responses in the liver and other affected organs of CF rabbits. In summary, our work demonstrates that sotagliflozin attenuates liver disorders in CF rabbits and suggests sotagliflozin as a potential drug to treat CFLD.
Xiubin Liang, Xia Hou, Mohamad Bouhamdan, Yifei Sun, Zhenfeng Song, Carthic Rajagopalan, Hong Jiang, Hong-Guang Wei, Jun Song, Dongshan Yang, Yanhong Guo, Yihan Zhang, Hongmei Mou, Jifeng Zhang, Y. Eugene Chen, Fei Sun, Jian-Ping Jin, Kezhong Zhang, Jie Xu
Usage data is cumulative from February 2024 through May 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 1,254 | 35 |
309 | 20 | |
Figure | 172 | 0 |
Table | 17 | 0 |
Supplemental data | 72 | 14 |
Citation downloads | 37 | 0 |
Totals | 1,861 | 69 |
Total Views | 1,930 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.