PMID- 25701721
OWN - NLM
STAT- MEDLINE
DCOM- 20160427
LR  - 20220409
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 754
DP  - 2015 May 5
TI  - Ipragliflozin, an SGLT2 inhibitor, exhibits a prophylactic effect on hepatic 
      steatosis and fibrosis induced by choline-deficient l-amino acid-defined diet in 
      rats.
PG  - 19-24
LID - S0014-2999(15)00104-1 [pii]
LID - 10.1016/j.ejphar.2015.02.009 [doi]
AB  - 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.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Hayashizaki-Someya, Yuka
AU  - Hayashizaki-Someya Y
AD  - Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki 305-8585, Japan. 
      Electronic address: yuka.hayashizaki@astellas.com.
FAU - Kurosaki, Eiji
AU  - Kurosaki E
AD  - Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki 305-8585, Japan.
FAU - Takasu, Toshiyuki
AU  - Takasu T
AD  - Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki 305-8585, Japan.
FAU - Mitori, Hikaru
AU  - Mitori H
AD  - Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki 305-8585, Japan.
FAU - Yamazaki, Shunji
AU  - Yamazaki S
AD  - Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki 305-8585, Japan.
FAU - Koide, Kumi
AU  - Koide K
AD  - Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki 305-8585, Japan.
FAU - Takakura, Shoji
AU  - Takakura S
AD  - Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki 305-8585, Japan.
LA  - eng
PT  - Journal Article
DEP - 20150219
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Amino Acids)
RN  - 0 (Glucosides)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Thiophenes)
RN  - 0 (Triglycerides)
RN  - 3N2N8OOR7X (ipragliflozin)
RN  - RMB44WO89X (Hydroxyproline)
RN  - X4OV71U42S (Pioglitazone)
SB  - IM
MH  - Amino Acids/pharmacology
MH  - Animals
MH  - Choline Deficiency/complications/*drug therapy/pathology
MH  - Food, Formulated/*adverse effects
MH  - Glucosides/*pharmacology/therapeutic use
MH  - Hydroxyproline/metabolism
MH  - Hypoglycemic Agents/pharmacology/therapeutic use
MH  - Inflammation/chemically induced/complications/prevention & control
MH  - Liver Cirrhosis/chemically induced/complications/pathology/*prevention & control
MH  - Male
MH  - Non-alcoholic Fatty Liver Disease/chemically 
      induced/complications/metabolism/*prevention & control
MH  - Pioglitazone
MH  - Rats
MH  - *Sodium-Glucose Transporter 2 Inhibitors
MH  - Thiazolidinediones/therapeutic use
MH  - Thiophenes/*pharmacology/therapeutic use
MH  - Triglycerides/metabolism
OTO - NOTNLM
OT  - Choline-deficient and amino acid-defined diet
OT  - Ipragliflozin l-proline (PubChem CID: 57339444)
OT  - Nonalcoholic fatty liver disease
OT  - Nonalcoholic steatohepatitis
OT  - Pioglitazone (PubChem CID: 4829)
OT  - SGLT2 inhibitor
EDAT- 2015/02/24 06:00
MHDA- 2016/04/28 06:00
CRDT- 2015/02/22 06:00
PHST- 2014/10/14 00:00 [received]
PHST- 2015/02/03 00:00 [revised]
PHST- 2015/02/10 00:00 [accepted]
PHST- 2015/02/22 06:00 [entrez]
PHST- 2015/02/24 06:00 [pubmed]
PHST- 2016/04/28 06:00 [medline]
AID - S0014-2999(15)00104-1 [pii]
AID - 10.1016/j.ejphar.2015.02.009 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2015 May 5;754:19-24. doi: 10.1016/j.ejphar.2015.02.009. Epub 
      2015 Feb 19.