Quistorff 2013 Abstract MiP2013
|Quistorff B (2013) With type 2 diabetes mitochondrial dysfunction develops earlier in liver than in skeletal muscle. Mitochondr Physiol Network 18.08.|
Quistorff B (2013)
Impaired mitochondrial function is implicated in the development of Type 2 diabetes mellitus (T2DM). This was investigated in mitochondria isolated from skeletal muscle and liver of the Gato-Kakizaki (GK) rat, which spontaneously develops T2DM with age. The early and the manifest stage of T2DM was studied in 6- and 16 weeks old GK rats, respectively.
In GK16 compared to GK6 animals, a decrease in OXPHOS capacity with palmitoyl carnitine (PC) as substrate was observed in muscle. Yet, an increase was seen in liver. To test the Complex II contribution to OXPHOS capacity, succinate was added together with PC. In liver mitochondria this resulted in a ~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 skeletal 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.
During the progression of T2DM in GK rats, liver mitochondria are affected differently and earlier than muscle mitochondria. Succinate dehydrogenase flux in the presence of fatty acids was severely reduced in liver but only marginally affected in muscle mitochondria during manifest T2DM. The observations support the notion that T2DM pathogenesis is initiated in the liver and only later muscle mitochondria are affected.
• O2k-Network Lab: DK Copenhagen Quistorff B
Labels: MiParea: Respiration, Comparative MiP;environmental MiP, mt-Medicine Pathology: Aging;senescence, Diabetes
Organism: Rat Tissue;cell: Skeletal muscle, Liver
Coupling state: LEAK, OXPHOS Pathway: F, S, Other combinations HRR: Oxygraph-2k
Dept Biomedical Sciences, NMR Center, University of Copenhagen, Denmark. - Email: firstname.lastname@example.org
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- Jørgensen W, Jelnes P, Rud KA, Hansen LL, Grunnet N, Quistorff B (2012) 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. Am J Physiol Endocrinol Metab 303: E515-E523.