PMID- 24425766
OWN - NLM
STAT- MEDLINE
DCOM- 20140527
LR  - 20211021
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 306
IP  - 6
DP  - 2014 Mar
TI  - Early mitochondrial dysfunction in glycolytic muscle, but not oxidative muscle, 
      of the fructose-fed insulin-resistant rat.
PG  - E658-67
LID - 10.1152/ajpendo.00511.2013 [doi]
AB  - Although evidence that type 2 diabetes mellitus (T2DM) is accompanied by 
      mitochondrial dysfunction in skeletal muscle has been accumulating, a causal link 
      between mitochondrial dysfunction and the pathogenesis of the disease remains 
      unclear. Our study focuses on an early stage of the disease to determine whether 
      mitochondrial dysfunction contributes to the development of T2DM. The 
      fructose-fed (FF) rat was used as an animal model of early T2DM. Mitochondrial 
      respiration and acylcarnitine species were measured in oxidative (soleus) and 
      glycolytic [extensor digitorum longus (EDL)] muscle. Although FF rats displayed 
      characteristic signs of T2DM, including hyperglycemia, hyperinsulinemia, and 
      hypertriglyceridemia, mitochondrial content was preserved in both muscles from FF 
      rats. The EDL muscle had reduced complex I and complex I and II respiration in 
      the presence of pyruvate but not glutamate. The decrease in pyruvate-supported 
      respiration was due to a decrease in pyruvate dehydrogenase activity. 
      Accumulation of C14:1 and C14:2 acylcarnitine species and a decrease in 
      respiration supported by long-chain acylcarnitines but not acetylcarnitine 
      indicated dysfunctional beta-oxidation in the EDL muscle. In contrast, the soleus 
      muscle showed preserved mitochondrial respiration, pyruvate dehydrogenase 
      activity, and increased fatty acid oxidation, as evidenced by overall reduced 
      acylcarnitine levels. Aconitase activity, a sensitive index of reactive oxygen 
      species production in mitochondria, was reduced exclusively in EDL muscle, which 
      showed lower levels of the antioxidant enzymes thioredoxin reductase and 
      glutathione peroxidase. Here, we show that the glycolytic EDL muscle is more 
      prone to an imbalance between energy supply and oxidation caused by insulin 
      resistance than the oxidative soleus muscle.
FAU - Warren, Blair E
AU  - Warren BE
AD  - Campus Saint-Jean, University of Alberta, Edmonton, Alberta, Canada;
FAU - Lou, Phing-How
AU  - Lou PH
FAU - Lucchinetti, Eliana
AU  - Lucchinetti E
FAU - Zhang, Liyan
AU  - Zhang L
FAU - Clanachan, Alexander S
AU  - Clanachan AS
FAU - Affolter, Andreas
AU  - Affolter A
FAU - Hersberger, Martin
AU  - Hersberger M
FAU - Zaugg, Michael
AU  - Zaugg M
FAU - Lemieux, Helene
AU  - Lemieux H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140114
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Dietary Carbohydrates)
RN  - 0 (Fatty Acids)
RN  - 0 (Pyruvate Dehydrogenase Complex)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (acylcarnitine)
RN  - 30237-26-4 (Fructose)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 8558G7RUTR (Pyruvic Acid)
RN  - EC 4.2.1.3 (Aconitate Hydratase)
RN  - S7UI8SM58A (Carnitine)
SB  - IM
EIN - Am J Physiol Endocrinol Metab. 2014 Dec 15;307(12):E1166
MH  - Aconitate Hydratase/metabolism
MH  - Animals
MH  - Carnitine/analogs & derivatives/metabolism
MH  - Diabetes Mellitus, Type 2/etiology/*metabolism/physiopathology
MH  - Dietary Carbohydrates/adverse effects
MH  - Disease Progression
MH  - Energy Metabolism
MH  - Fatty Acids/metabolism
MH  - Fructose/adverse effects
MH  - Glutamic Acid/metabolism
MH  - *Glycolysis
MH  - *Insulin Resistance
MH  - Male
MH  - Mitochondria, Muscle/*metabolism
MH  - Muscle, Skeletal/*metabolism
MH  - *Oxidative Phosphorylation
MH  - Prediabetic State/etiology/*metabolism/physiopathology
MH  - Pyruvate Dehydrogenase Complex/metabolism
MH  - Pyruvic Acid/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
PMC - PMC3948982
OTO - NOTNLM
OT  - aconitase
OT  - fatty acid oxidation
OT  - insulin resistance
OT  - mitochondrial dysfunction
OT  - sirtuin-3
OT  - skeletal muscle
OT  - type 2 diabetes
EDAT- 2014/01/16 06:00
MHDA- 2014/05/28 06:00
PMCR- 2015/03/15
CRDT- 2014/01/16 06:00
PHST- 2014/01/16 06:00 [entrez]
PHST- 2014/01/16 06:00 [pubmed]
PHST- 2014/05/28 06:00 [medline]
PHST- 2015/03/15 00:00 [pmc-release]
AID - ajpendo.00511.2013 [pii]
AID - E-00511-2013 [pii]
AID - 10.1152/ajpendo.00511.2013 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2014 Mar;306(6):E658-67. doi: 
      10.1152/ajpendo.00511.2013. Epub 2014 Jan 14.