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This Article Full Text (PDF) Free All Versions of this Article: 101/6/1810    most recent 01080.2006v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wasserman, D. H. Articles by Fueger, P. T. Search for Related Content PubMed Articles by Wasserman, D. H. Articles by Fueger, P. T.

Last Word: Point:Counterpoint author responds to commentaries on "Glucose phosphorylation is/is not a significant barrier to muscle glucose uptake by the working muscle"

Department of Molecular Physiology and Biophysics and Mouse Metabolic Phenotyping Center
Vanderbilt University School of Medicine
Sarah W. Stedman Nutrition and Metabolism Center and Department of Pharmacology and Cancer Biology
Duke University Medical Center

To the Editor: We completely agree with the points brought forth by Dr. Katz (3). His point that the measurement of muscle glucose may be insensitive to several-fold increases in intracellular free glucose is a particularly important consideration. The points brought forth by Drs. Richter, Rose, Wojtaszewski, and Hargreaves (3) require clarification. We agree with Dr. Richter and colleagues that caution must be taken in extrapolating data obtained in mice to humans. Application of conclusions from any animal model to humans must be made with caution. Animal models, of course, are necessary to gain a perspective that cannot be obtained from studies in human subjects. The studies in humans that can be used to address whether glucose phosphorylation is a barrier to muscle glucose uptake during exercise generally support results from studies in the mouse showing that it is. Thus it is unnecessary to invoke species differences in this specific case because data from humans are consistent with conclusions drawn from mouse models. That is not to say that there are not instances such as light exercise or exercise in glycogen-depleted (low glucose 6-phosphate) states where phosphorylation is not a barrier to muscle glucose uptake. This may very well be the case.

So how then do Dr. Richter and colleagues draw the conclusion "regarding exercise in humans...glucose transport limits glucose uptake in most exercise conditions" (3)? As emphasized by Dr. Katz (3), there are few data to support this assertion. Dr. Richter and colleagues find the argument convincing that K_m for glucose uptake during exercise does not reflect contribution from hexokinase. But as far as we are aware, the only value reported for K_m of muscle glucose uptake in exercising human subjects is one reported in a review article by Rose and Richter (4). This single value for K_m is difficult to make sense of because the K_m and V_max reported in the legend to Figure 3 in the review (4) appears to vastly overestimate the values from the graph in Figure 3. This is also discussed in section 4 of our rebuttal to Drs. Ploug and Vinton. In formulating their view, Richter and colleagues seem to neglect the compelling and unambiguous data present in Table 3 of Richter et al. (2) that shows a two- to threefold increase in muscle glucose during moderate exercise (40 min of exercise at an oxygen uptake of <2 l/min). As stated in our rebuttal to Drs. Ploug and Vinton, the paper of Richter et al. (2) strongly supports the assertion that glucose phosphorylation is a barrier to muscle glucose uptake during exercise in humans (5).

REFERENCES

1. Ploug T and Vinten J. Counterpoint: Glucose phosphorylation is not a significant barrier to muscle glucose uptake by the working muscle. J Appl Physiol. In press.
2. Richter EA, Jensen P, Kiens B, and Kristiansen S. Sarcolemmal glucose transport and GLUT-4 translocation during exercise are diminished by endurance training. Am J Physiol Endocrinol Metab 274: E89–E95, 1998.[Abstract/Free Full Text]
3. Richter EA, Rose AJ, Wojtaszewski JFP, Hargreaves M, and Katz A. Comments on Point:Counterpoint: Glucose phosphorylation is/is not a significant barrier to muscle glucose uptake by the working muscle. J Appl Physiol. In press.
4. Rose AJ and Richter EA. Skeletal muscle glucose uptake during exercise: how is it regulated? Physiology 20: 260–270, 2005.[Abstract/Free Full Text]
5. Wasserman DH and Fueger PT. Point: Glucose phosphorylation is a significant barrier to muscle glucose uptake by the working muscle. J Appl Physiol. In press.

This Article Full Text (PDF) Free All Versions of this Article: 101/6/1810    most recent 01080.2006v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wasserman, D. H. Articles by Fueger, P. T. Search for Related Content PubMed Articles by Wasserman, D. H. Articles by Fueger, P. T.