Abstract |
Ipragliflozin is a selective sodium glucose cotransporter 2 ( SGLT2) inhibitor that increases urinary glucose excretion by inhibiting renal glucose reabsorption and thereby causes a subsequent antihyperglycemic effect. As nonalcoholic fatty liver disease ( NAFLD), including nonalcoholic steatohepatitis (NASH), is closely linked to metabolic diseases such as obesity and diabetes, we investigated the effect of ipragliflozin on NAFLD in rats fed a choline-deficient l- amino acid-defined ( CDAA) diet. Five weeks after starting the CDAA diet, rats exhibited hepatic triglyceride (TG) accumulation, fibrosis, and mild inflammation. Repeated oral administration of ipragliflozin (3mg/g, once daily for 5 weeks) prevented both hepatic TG accumulation (188 vs.290 mg/g tissue vehicle-treated group; P<0.001) and large lipid droplet formation. Further, ipragliflozin exerted a prophylactic effect on liver fibrosis, as indicated by a marked decrease in hydroxyproline content and fibrosis score. Pioglitazone, which is known to be effective on hepatic fibrosis in CDAA diet-fed rats as well as NASH patients with type 2 diabetes mellitus (T2DM), also exerted a mild prophylactic effect on fibrosis, but not on hepatic TG accumulation or inflammation. In conclusion, ipragliflozin prevented hepatic TG accumulation and fibrosis in CDAA-diet rats. These findings suggest the therapeutic potential of ipragliflozin for patients with NAFLD.
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Authors | Yuka Hayashizaki-Someya, Eiji Kurosaki, Toshiyuki Takasu, Hikaru Mitori, Shunji Yamazaki, Kumi Koide, Shoji Takakura |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 754
Pg. 19-24
(May 05 2015)
ISSN: 1879-0712 [Electronic] Netherlands |
PMID | 25701721
(Publication Type: Journal Article)
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Copyright | Copyright © 2015 Elsevier B.V. All rights reserved. |
Chemical References |
- Amino Acids
- Glucosides
- Hypoglycemic Agents
- Sodium-Glucose Transporter 2 Inhibitors
- Thiazolidinediones
- Thiophenes
- Triglycerides
- ipragliflozin
- Hydroxyproline
- Pioglitazone
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Topics |
- Amino Acids
(pharmacology)
- Animals
- Choline Deficiency
(complications, drug therapy, pathology)
- Food, Formulated
(adverse effects)
- Glucosides
(pharmacology, therapeutic use)
- Hydroxyproline
(metabolism)
- Hypoglycemic Agents
(pharmacology, therapeutic use)
- Inflammation
(chemically induced, complications, prevention & control)
- Liver Cirrhosis
(chemically induced, complications, pathology, prevention & control)
- Male
- Non-alcoholic Fatty Liver Disease
(chemically induced, complications, metabolism, prevention & control)
- Pioglitazone
- Rats
- Sodium-Glucose Transporter 2 Inhibitors
- Thiazolidinediones
(therapeutic use)
- Thiophenes
(pharmacology, therapeutic use)
- Triglycerides
(metabolism)
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