What Do Magnetic Resonance–Based Measurements of Pi→ATP Flux Tell Us About Skeletal Muscle Metabolism?

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FIG. 2.
FIG. 2.

Resting muscle Pi→ATP flux and oxidative ATP synthesis rate in IR and insulin stimulation: a quantitative summary of the literature. The figure shows (in logarithmic form) mean values from published studies of Pi→ATP flux measured by 31P MRS MT (circles) and oxidative ATP synthesis rate calculated from published 13C MRS measurements of TCAC rate (triangles) and from AVD measurements of muscle O2 consumption (diamonds). Each linked pair of points shows the means in single reported studies. A compares control muscle in the fasting state and during hyperinsulinemic-euglycemic clamp, and B compares control and IR states. In both, each linked pair of points represents mean values of basal versus insulin or control versus IR from a single study. Filled symbols show that the difference was statistically significant within the study, and open symbols that it was not. Studies in A are: MT measurements (23,25,28,31,32) and AVD measurements (4751). [Pi→ATP flux is also stimulated by insulin in Petersen et al. (19), not plotted in the figure because absolute rates are not reported.] Studies in B are: MT measurements in mitochondrial diabetes (myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) (25), type 2 diabetic patients (3,23,28,31), and their first-degree relatives (20,30), women with a history of gestational diabetes (24), patients with inherited insulin receptor signaling defects (1), and elderly (versus young) subjects (16); 13C MRS measurements in elderly (versus young) subjects (16) and first-degree relatives of type 2 diabetic patients (12); and AVD measurements in type 2 diabetic patients (49,50). Note that for the AVD and 13C MRS measurements in this figure, we have assumed that neither insulin nor type 2 diabetes affects the P:O ratio. This is unlikely to be so; if there were no proton leak across the inner mitochondrial membrane, then for stoichiometric reasons, the P:O ratio for glucose oxidation would be ∼10–15% higher than for palmitate oxidation (38); thus, the insulin-induced switch from fat to glucose oxidation (4751) would increase P:O. However, effective P:O ratios in vivo are influenced (lowered) by significant proton leak (38), and it is unknown how this changes in response to insulin or in type 2 diabetes.

This Article

  1. Diabetes vol. 61 no. 8 1927-1934