Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle

Journal article

Lee-Young, Robert S., Hoffman, Nolan John, Murphy, Kate T., Henstridge, Darren C., Samocha-Bonet, Dorit, Siebel, Andrew L., Iliades, Peter, Zivanovic, Borivoj, Hong, Yet H., Colgan, Timothy D., Kraakman, Michael J., Bruce, Clinton R., Gregorevic, Paul, McConell, Glenn K., Lynch, Gordon S., Drummond, Grant R., Kingwell, Bronwyn A., Greenfield, Jerry R. and Febbraio, Mark A.. (2016). Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle. Molecular Metabolism. 5(11), pp. 1083 - 1091. https://doi.org/10.1016/j.molmet.2016.09.002
AuthorsLee-Young, Robert S., Hoffman, Nolan John, Murphy, Kate T., Henstridge, Darren C., Samocha-Bonet, Dorit, Siebel, Andrew L., Iliades, Peter, Zivanovic, Borivoj, Hong, Yet H., Colgan, Timothy D., Kraakman, Michael J., Bruce, Clinton R., Gregorevic, Paul, McConell, Glenn K., Lynch, Gordon S., Drummond, Grant R., Kingwell, Bronwyn A., Greenfield, Jerry R. and Febbraio, Mark A.
Abstract

Objective: The development of skeletal muscle insulin resistance is an early physiological defect, yet the intracellular mechanisms accounting for this metabolic defect remained unresolved. Here, we have examined the role of glucose-6-phosphate dehydrogenase (G6PDH) activity in the pathogenesis of insulin resistance in skeletal muscle. Methods: Multiple mouse disease states exhibiting insulin resistance and glucose intolerance, as well as obese humans defined as insulin-sensitive, insulin-resistant, or pre-diabetic, were examined. Results: We identified increased glucose-6-phosphate dehydrogenase (G6PDH) activity as a common intracellular adaptation that occurs in parallel with the induction of insulin resistance in skeletal muscle and is present across animal and human disease states with an underlying pathology of insulin resistance and glucose intolerance. We observed an inverse association between G6PDH activity and nitric oxide synthase (NOS) activity and show that increasing NOS activity via the skeletal muscle specific neuronal (n)NOSμ partially suppresses G6PDH activity in skeletal muscle cells. Furthermore, attenuation of G6PDH activity in skeletal muscle cells via (a) increased nNOSμ/NOS activity, (b) pharmacological G6PDH inhibition, or (c) genetic G6PDH inhibition increases insulin-independent glucose uptake. Conclusions: We have identified a novel, previously unrecognized role for G6PDH in the regulation of skeletal muscle glucose metabolism.

Year2016
JournalMolecular Metabolism
Journal citation5 (11), pp. 1083 - 1091
PublisherElsevier GmbH
ISSN2212-8778
Digital Object Identifier (DOI)https://doi.org/10.1016/j.molmet.2016.09.002
Scopus EID2-s2.0-84994714152
Open accessOpen access
Page range1083 - 1091
Research GroupMary MacKillop Institute for Health Research
Publisher's version
Additional information

© 2016 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Place of publicationGermany
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