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

Lee-Young, Robert S., Hoffman, Nolan J, 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, 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, vol. 5, no. 11, pp. 1083-1091, doi: 10.1016/j.molmet.2016.09.002.

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Title Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle
Author(s) Lee-Young, Robert S.
Hoffman, Nolan J
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, ClintonORCID iD for Bruce, Clinton
Gregorevic, Paul
McConell, Glenn K.
Lynch, Gordon S.
Drummond, Grant R.
Kingwell, Bronwyn A.
Greenfield, Jerry R.
Febbraio, Mark A.
Journal name Molecular metabolism
Volume number 5
Issue number 11
Start page 1083
End page 1091
Total pages 9
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2016-11
ISSN 2212-8778
Keyword(s) Glucose-6-phosphate
glucose uptake
skeletal muscle
Summary 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.

Language eng
DOI 10.1016/j.molmet.2016.09.002
Field of Research 110199 Medical Biochemistry and Metabolomics not elsewhere classified
Socio Economic Objective 920104 Diabetes
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2016, Elsevier
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Document type: Journal Article
Collection: School of Exercise and Nutrition Sciences
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