In:
Diabetes, American Diabetes Association, Vol. 70, No. Supplement_1 ( 2021-06-01)
Abstract:
Nonalcoholic steatohepatitis (NASH) is the most prevalent chronic liver disease worldwide and increases the risk for hepatocellular carcinoma (HCC) in developed countries. However, no medications have been approved to protect against NASH-driven HCC. Dapagliflozin, a sodium glucose cotransporter-2 (SGLT-2) inhibitor, improves hyperglycemia by promoting glycosuria. We investigated whether dapagliflozin prevents NASH-driven HCC using a mouse model. Diethylnitrosamine (25 mg/kg) was intraperitoneally injected into 2-week-old C57BL6/J male mice, followed by either normal chow diet or 60% high-fat diet (HFD) for 30 weeks with or without dapagliflozin, 0.003% (w/w). HFD-fed mice without dapagliflozin had an increased number of tumor on liver surface compared with chow-fed mice (77.0 vs. 12.5/per mouse; n=6 per group; p=0.01). The number of liver tumors was significantly lower in dapagliflozin treated group (19.5/per mouse in dapagliflozin-treated HFD-fed mice; n=6) than that in HFD-fed mice without dapagliflozin (p=0.03). Dapagliflozin treatment numerically reduced body weight and fasting blood glucose compared with HFD-fed mice without dapagliflozin (41.0 vs. 40.2 g, p=0.94 for body weight, and 196.3 vs. 170.8 mg/dL, p=0.34 for fasting blood glucose). In addition, several human HCC cell lines (Huh 7, HepG2, and Hep3B) expressed SGLT-2 protein. Thus, it is possible that dapagliflozin might directly modulate HCC development via SGLT-2 inhibition. In conclusion, dapagliflozin attenuates NASH-associated HCC development possibly via its direct effect on HCC. Disclosure M. Lee: None. H. Lee: None. E. Kang: None. Y. Kim: None. S. Lee: None. H. Kim: None. S. Lee: None. J. Kim: None. S. Kim: None. R. Kim: None. H. Park: None.
Type of Medium:
Online Resource
ISSN:
0012-1797
,
1939-327X
Language:
English
Publisher:
American Diabetes Association
Publication Date:
2021
detail.hit.zdb_id:
1501252-9
