PMID- 22713504
OWN - NLM
STAT- MEDLINE
DCOM- 20121119
LR  - 20120816
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Linking)
VI  - 303
IP  - 4
DP  - 2012 Aug 15
TI  - Progression of type 2 diabetes in GK rats affects muscle and liver mitochondria 
      differently: pronounced reduction of complex II flux is observed in liver only.
PG  - E515-23
LID - 10.1152/ajpendo.00103.2012 [doi]
AB  - Impaired mitochondrial function is implicated in the development of type 2 
      diabetes mellitus (T2DM). This was investigated in mitochondria from skeletal 
      muscle and liver of the Goto-Kakizaki (GK) rat, which spontaneously develops T2DM 
      with age. The early and the manifest stage of T2DM was studied in 6- and 
      16-wk-old GK rats, respectively. In GK16 compared with GK6 animals, a decrease in 
      state 3 respiration with palmitoyl carnitine (PC) as substrate was observed in 
      muscle. Yet an increase was seen in liver. To test the complex II contribution to 
      the state 3 respiration, succinate was added together with PC. In liver 
      mitochondria, this resulted in an  approximately 50% smaller respiratory increase in the GK6 
      group compared with control and no respiratory increase at all in the GK16 
      animals. Yet no difference between groups was seen in muscle mitochondria. RCR 
      and P/O ratio was increased (P < 0.05) in liver but unchanged in muscle in both 
      GK groups. We observed increased lipid peroxidation and decreased Akt 
      phosphorylation in liver with the progression of T2DM but no change in muscle. We 
      conclude that, during the progression of T2DM in GK rats, liver mitochondria are 
      affected earlier and/or more severely than muscle mitochondria. Succinate 
      dehydrogenase flux in the presence of fatty acids was reduced severely in liver 
      but not in muscle mitochondria during manifest T2DM. The observations support the 
      notion that T2DM pathogenesis is initiated in the liver and that only later are 
      muscle mitochondria affected.
FAU - Jorgensen, Wenche
AU  - Jorgensen W
AD  - Dept. of Biomedical Sciences, NMR Center, Univ. of Copenhagen, Faculty of Health 
      Sciences, Blegdamsvej 3, 2200 Copenhagen, Denmark.
FAU - Jelnes, Peter
AU  - Jelnes P
FAU - Rud, Kasper A
AU  - Rud KA
FAU - Hansen, Lillian L
AU  - Hansen LL
FAU - Grunnet, Niels
AU  - Grunnet N
FAU - Quistorff, Bjorn
AU  - Quistorff B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120619
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 1935-18-8 (Palmitoylcarnitine)
RN  - EC 1.3.5.1 (Electron Transport Complex II)
RN  - EC 1.3.99.1 (Succinate Dehydrogenase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/enzymology/*physiopathology
MH  - Disease Progression
MH  - Electron Transport Complex II/*metabolism
MH  - Lipid Peroxidation
MH  - Male
MH  - Mitochondria, Liver/*enzymology
MH  - Mitochondria, Muscle/*enzymology
MH  - Oxygen Consumption
MH  - Palmitoylcarnitine/metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Severity of Illness Index
MH  - Succinate Dehydrogenase/metabolism
EDAT- 2012/06/21 06:00
MHDA- 2012/12/10 06:00
CRDT- 2012/06/21 06:00
PHST- 2012/06/21 06:00 [entrez]
PHST- 2012/06/21 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - ajpendo.00103.2012 [pii]
AID - 10.1152/ajpendo.00103.2012 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2012 Aug 15;303(4):E515-23. doi: 
      10.1152/ajpendo.00103.2012. Epub 2012 Jun 19.