Difference between revisions of "Yu 2013 Diabetes"
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|injuries=Oxidative stress;RONS | |injuries=Oxidative stress;RONS | ||
|diseases=Diabetes | |diseases=Diabetes | ||
|topics=ATP | |topics=ATP, ATP production | ||
|couplingstates=LEAK, OXPHOS | |couplingstates=LEAK, OXPHOS | ||
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Revision as of 10:03, 27 November 2015
Yu L, Fink BD, Herlein JA, Sivitz WI (2013) Mitochondrial function in diabetes: novel methodology and new insight. Diabetes 62:1833-42. |
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 ΞΞ¨, enabling more detailed study. We used a 2-deoxyglucose (2DOG) energy clamp to set ΞΞ¨ 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 ΞΞ¨ 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. β’ Keywords: Diabetes, Heteronuclear single-quantum coherence nuclear magnetic resonance spectroscopy, Amplex Red, TPP electrode
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, mt-Medicine
Pathology: Diabetes
Stress:Oxidative stress;RONS
Organism: Rat
Tissue;cell: Skeletal muscle
Preparation: Isolated mitochondria
Regulation: ATP, ATP production Coupling state: LEAK, OXPHOS