1170-P: Dapagliflozin, a Sodium Glucose Cotransporter 2 Inhibitor, Attenuates the Development of Nonalcoholic Steatohepatitis-Associated Hepatocellular Carcinoma
| Autor: | Ryeong-Hyeon Kim, Sejeong Lee, Youngeun Kim, Min Young Lee, Eun Seok Kang, Sun-Woo Kim, Hae Kyung Kim, Hyunki Park, Hayngkyu Lee, Jiwon Kim, Sook Jung Lee |
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| Rok vydání: | 2021 |
| Předmět: |
Glycosuria
Nonalcoholic steatohepatitis medicine.medical_specialty Treated group business.industry Endocrinology Diabetes and Metabolism Chronic liver disease medicine.disease Body weight digestive system diseases chemistry.chemical_compound Endocrinology chemistry Internal medicine Hepatocellular carcinoma Internal Medicine medicine Sodium-Glucose Cotransporter 2 Inhibitor medicine.symptom Dapagliflozin business |
| Zdroj: | Diabetes. 70 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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