PMID- 21820301
OWN - NLM
STAT- MEDLINE
DCOM- 20121102
LR  - 20220410
IS  - 1873-4847 (Electronic)
IS  - 0955-2863 (Linking)
VI  - 23
IP  - 7
DP  - 2012 Jul
TI  - Enhanced autophagy plays a cardinal role in mitochondrial dysfunction in type 2 
      diabetic Goto-Kakizaki (GK) rats: ameliorating effects of 
      (-)-epigallocatechin-3-gallate.
PG  - 716-24
LID - 10.1016/j.jnutbio.2011.03.014 [doi]
AB  - Oxidative stress and mitochondrial dysfunction are known to play important roles 
      in type 2 diabetes mellitus (T2DM) and insulin resistance. However, the pathology 
      of T2DM remains complicated; in particular, the mechanisms of mitochondrial 
      dysfunction in skeletal muscle and other insulin-sensitive tissues are as yet 
      unclear. In the present study, we investigated the underlying mechanisms of 
      oxidative stress and mitochondrial dysfunction by focusing on mitochondrial 
      dynamics, including mitochondrial biogenesis and autophagy, in skeletal muscle of 
      a nonobese diabetic animal model--the Goto-Kakizaki (GK) rat. The results showed 
      that GK rats exhibited impaired glucose metabolism, increased oxidative stress 
      and decreased mitochondrial function. These dysfunctions were found to be 
      associated with induction of LC3B, Beclin1 and DRP1 (key molecules mediating the 
      autophagy pathway), while they appeared not to affect the mitochondrial 
      biogenesis pathway. In addition, (-)-epigallocatechin-3-gallate (EGCG) was tested 
      as a potential autophagy-targeting nutrient, and we found that EGCG treatment 
      improved glucose tolerance and glucose homeostasis in GK rats, and reduced 
      oxidative stress and mitochondrial dysfunction in skeletal muscle. Amelioration 
      of excessive muscle autophagy in GK rats through the down-regulation of the 
      ROS-ERK/JNK-p53 pathway leads to improvement of glucose metabolism, reduction of 
      oxidative stress and inhibition of mitochondrial loss and dysfunction. These 
      results suggest (a) that hyperglycemia-associated oxidative stress may induce 
      autophagy through up-regulation of the ROS-ERK/JNK-p53 pathway, which may 
      contribute to mitochondrial loss in soleus muscle of diabetic GK rats, and (b) 
      that EGCG may be a potential autophagy regulator useful in treatment of insulin 
      resistance.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Yan, Jiong
AU  - Yan J
AD  - Department of Biology and Engineering, Institute of Mitochondrial Biology and 
      Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of 
      Education, Xi'an Jiaotong University School of Life Science and Technology, Xi'an 
      710049, China.
FAU - Feng, Zhihui
AU  - Feng Z
FAU - Liu, Jia
AU  - Liu J
FAU - Shen, Weili
AU  - Shen W
FAU - Wang, Ying
AU  - Wang Y
FAU - Wertz, Karin
AU  - Wertz K
FAU - Weber, Peter
AU  - Weber P
FAU - Long, Jiangang
AU  - Long J
FAU - Liu, Jiankang
AU  - Liu J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110804
PL  - United States
TA  - J Nutr Biochem
JT  - The Journal of nutritional biochemistry
JID - 9010081
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 8R1V1STN48 (Catechin)
RN  - BQM438CTEL (epigallocatechin gallate)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Blood Glucose
MH  - Catechin/*analogs & derivatives/pharmacology
MH  - Diabetes Mellitus, Type 2/drug therapy/metabolism/*physiopathology
MH  - Down-Regulation
MH  - Fasting
MH  - Hypoglycemic Agents/*pharmacology
MH  - Insulin Resistance
MH  - Male
MH  - Mitochondria/*drug effects/metabolism
MH  - Mitogen-Activated Protein Kinases/genetics/metabolism
MH  - Muscle, Skeletal/drug effects/metabolism/physiopathology
MH  - Oxidative Stress/*drug effects
MH  - Rats
MH  - Tumor Suppressor Protein p53/genetics/metabolism
MH  - Up-Regulation
EDAT- 2011/08/09 06:00
MHDA- 2012/11/03 06:00
CRDT- 2011/08/09 06:00
PHST- 2010/10/02 00:00 [received]
PHST- 2011/03/15 00:00 [revised]
PHST- 2011/03/17 00:00 [accepted]
PHST- 2011/08/09 06:00 [entrez]
PHST- 2011/08/09 06:00 [pubmed]
PHST- 2012/11/03 06:00 [medline]
AID - S0955-2863(11)00111-2 [pii]
AID - 10.1016/j.jnutbio.2011.03.014 [doi]
PST - ppublish
SO  - J Nutr Biochem. 2012 Jul;23(7):716-24. doi: 10.1016/j.jnutbio.2011.03.014. Epub 
      2011 Aug 4.