Yu 2013 Diabetes: Difference between revisions
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|diseases=Diabetes | |diseases=Diabetes | ||
| | |topics=ATP; ADP; AMP; PCr | ||
|couplingstates=LEAK, OXPHOS | |couplingstates=LEAK, OXPHOS | ||
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Revision as of 15:41, 12 August 2013
Yu L, Fink BD, Herlein JA, Sivitz WI (2013) Mitochondrial function in diabetes: novel methodology and new insight. Diabetes [Epub ahead of print]. |
Yu L, Fink BD, Herlein JA, Sivitz WI (2013) Diabetes
Abstract: Interpreting mitochondrial function as affected by comparative physiologic conditions is confounding because individual functional parameters are interdependent. Here, we studied muscle mitochondrial function in insulin-deficient diabetes using a novel, highly sensitive, and specific method to quantify ATP production simultaneously with reactive oxygen species (ROS) at clamped levels of ฮฮจ, enabling more detailed study. We used a 2-deoxyglucose (2DOG) energy clamp to set ฮฮจ at fixed levels and to quantify ATP production as 2DOG conversion to 2DOG-phosphate measured by one-dimensional (1)H and two-dimensional (1)H/(13)C heteronuclear single-quantum coherence nuclear magnetic resonance spectroscopy. These techniques proved far more sensitive than conventional (31)P nuclear magnetic resonance and allowed high-throughput study of small mitochondrial isolates. Over conditions ranging from state 4 to state 3 respiration, ATP production was lower and ROS per unit of ATP generated was greater in mitochondria isolated from diabetic muscle. Moreover, ROS began to increase at a lower threshold for inner membrane potential in diabetic mitochondria. Further, ATP production in diabetic mitochondria is limited not only by respiration but also by limited capacity to use ฮฮจ for ATP synthesis. In summary, we describe novel methodology for measuring ATP and provide new mechanistic insight into the dysregulation of ATP production and ROS in mitochondria of insulin-deficient rodents. โข Keywords: Diabetes, Heteronuclear single-quantum coherence nuclear magnetic resonance spectroscopy
Labels:
Pathology: Diabetes
Stress:RONS; Oxidative Stress"RONS; Oxidative Stress" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property.
Organism: Rat
Tissue;cell: Skeletal muscle
Regulation: ATP; ADP; AMP; PCr"ATP; ADP; AMP; PCr" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
Coupling state: LEAK, OXPHOS
Epub ahead of print