PMID- 26773928
OWN - NLM
STAT- MEDLINE
DCOM- 20160524
LR  - 20181202
IS  - 1532-8600 (Electronic)
IS  - 0026-0495 (Linking)
VI  - 65
IP  - 2
DP  - 2016 Feb
TI  - Treatment with atorvastatin attenuates progression of insulin resistance and 
      pancreatic fibrosis in the Otsuka Long-Evans Tokushima fatty rats.
PG  - 41-53
LID - S0026-0495(15)00304-2 [pii]
LID - 10.1016/j.metabol.2015.10.012 [doi]
AB  - PURPOSE: The effects of statins on insulin resistance (IR) and type 2 diabetes 
      mellitus (T2DM) are still controversial and its effects on pancreatic fibrosis 
      are poorly defined. The purpose of this study is to examine the effects of 
      atorvastatin on these issues using the Otsuka Long-Evans Tokushima Fatty (OLETF) 
      rat, an animal model of IR, T2DM and pancreatic fibrosis. METHODS: Male OLETF 
      rats were divided into 2 groups at 6weeks of age. The first group received a 
      standard diet until the end of experimental period at age 28weeks. The second 
      group was given a diet containing 0.05% atorvastatin from 6weeks of age, before 
      the onset of IR and pancreatic fibrosis. The age-matched Long-Evans Tokushima 
      Otsuka rats without presence of IR, T2DM and pancreatic fibrosis, received a 
      standard diet and were used as a normal control. RESULTS: Atorvastatin slightly 
      decreased serum fasting glucose and insulin levels, but significantly improved 
      index of IR compared with the untreated OLETF rats. In addition, atorvastatin 
      markedly decreased transforming growth factor-beta1 mRNA expression, myeloperoxidase 
      activity and proportion of fibrotic area, and elevated superoxide dismutase 
      activity in the pancreas compared with the untreated OLETF rats. CONCLUSIONS: 
      These findings suggest that atorvastatin exerts favorable influence on 
      progression of IR and pancreatic inflammation and fibrosis via pleiotropic effect 
      such as anti-oxidative property.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Wei, Limin
AU  - Wei L
AD  - The Third Department of Internal Medicine, University of Occupational and 
      Environmental Health, School of Medicine, Kitakyushu, Japan.
FAU - Yamamoto, Mitsuyoshi
AU  - Yamamoto M
AD  - The Third Department of Internal Medicine, University of Occupational and 
      Environmental Health, School of Medicine, Kitakyushu, Japan. Electronic address: 
      m-yamamo@med.uoeh-u.ac.jp.
FAU - Harada, Masaru
AU  - Harada M
AD  - The Third Department of Internal Medicine, University of Occupational and 
      Environmental Health, School of Medicine, Kitakyushu, Japan.
FAU - Otsuki, Makoto
AU  - Otsuki M
AD  - The Third Department of Internal Medicine, University of Occupational and 
      Environmental Health, School of Medicine, Kitakyushu, Japan; Department of 
      Internal Medicine, Kitasuma Hospital, Kobe, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151009
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Antioxidants)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Transforming Growth Factor beta1)
RN  - A0JWA85V8F (Atorvastatin)
SB  - IM
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Apoptosis/drug effects
MH  - Atorvastatin/*pharmacology
MH  - Body Weight/drug effects
MH  - Eating/drug effects
MH  - Fibrosis
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - *Insulin Resistance
MH  - Male
MH  - Oxidative Stress/drug effects
MH  - Pancreas/*drug effects/pathology
MH  - Rats
MH  - Rats, Inbred OLETF
MH  - Transforming Growth Factor beta1/genetics
OTO - NOTNLM
OT  - Atorvastatin
OT  - Insulin resistance
OT  - OLETF rat
OT  - Pancreatic fibrosis
EDAT- 2016/01/17 06:00
MHDA- 2016/05/25 06:00
CRDT- 2016/01/17 06:00
PHST- 2015/01/26 00:00 [received]
PHST- 2015/09/20 00:00 [revised]
PHST- 2015/10/01 00:00 [accepted]
PHST- 2016/01/17 06:00 [entrez]
PHST- 2016/01/17 06:00 [pubmed]
PHST- 2016/05/25 06:00 [medline]
AID - S0026-0495(15)00304-2 [pii]
AID - 10.1016/j.metabol.2015.10.012 [doi]
PST - ppublish
SO  - Metabolism. 2016 Feb;65(2):41-53. doi: 10.1016/j.metabol.2015.10.012. Epub 2015 
      Oct 9.