Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle
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 i...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-11-01
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| Series: | Molecular Metabolism |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877816301338 |
| _version_ | 1811271866386481152 |
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| author | Robert S. Lee-Young Nolan J. Hoffman Kate T. Murphy Darren C. Henstridge Dorit Samocha-Bonet Andrew L. Siebel Peter Iliades Borivoj Zivanovic Yet H. Hong Timothy D. Colgan Michael J. Kraakman Clinton R. Bruce Paul Gregorevic Glenn K. McConell Gordon S. Lynch Grant R. Drummond Bronwyn A. Kingwell Jerry R. Greenfield Mark A. Febbraio |
| author_facet | Robert S. Lee-Young Nolan J. Hoffman Kate T. Murphy Darren C. Henstridge Dorit Samocha-Bonet Andrew L. Siebel Peter Iliades Borivoj Zivanovic Yet H. Hong Timothy D. Colgan Michael J. Kraakman Clinton R. Bruce Paul Gregorevic Glenn K. McConell Gordon S. Lynch Grant R. Drummond Bronwyn A. Kingwell Jerry R. Greenfield Mark A. Febbraio |
| author_sort | Robert S. Lee-Young |
| collection | DOAJ |
| description | 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. Author Video: Author Video Watch what authors say about their articles Keywords: Glucose metabolism, Enzyme activity, Insulin sensitivity |
| first_indexed | 2024-04-12T22:29:50Z |
| format | Article |
| id | doaj.art-b7a0d2f504b14b63ab5ea39dfdc8387f |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-04-12T22:29:50Z |
| publishDate | 2016-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-b7a0d2f504b14b63ab5ea39dfdc8387f2022-12-22T03:14:01ZengElsevierMolecular Metabolism2212-87782016-11-0151110831091Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscleRobert S. Lee-Young0Nolan J. Hoffman1Kate T. Murphy2Darren C. Henstridge3Dorit Samocha-Bonet4Andrew L. Siebel5Peter Iliades6Borivoj Zivanovic7Yet H. Hong8Timothy D. Colgan9Michael J. Kraakman10Clinton R. Bruce11Paul Gregorevic12Glenn K. McConell13Gordon S. Lynch14Grant R. Drummond15Bronwyn A. Kingwell16Jerry R. Greenfield17Mark A. Febbraio18Cellular and Molecular Metabolism Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, Australia; Corresponding author. Mouse Metabolic Phenotyping Facility, Metabolic Disease and Obesity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.Diabetes & Metabolism Division, Garvan Institute of Medical Research, NSW, AustraliaBasic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Melbourne, VIC, AustraliaCellular and Molecular Metabolism Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, AustraliaDiabetes & Metabolism Division, Garvan Institute of Medical Research, NSW, AustraliaMetabolic and Vascular Physiology Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, AustraliaCellular and Molecular Metabolism Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, AustraliaCellular and Molecular Metabolism Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, AustraliaInstitute for Sports, Exercise and Active Living, Victoria University, Footscray, VIC, AustraliaMuscle Research and Therapeutics Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, AustraliaCellular and Molecular Metabolism Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, AustraliaSchool of Exercise and Nutrition Sciences, Deakin University, Burwood, VIC, AustraliaMuscle Research and Therapeutics Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, AustraliaInstitute for Sports, Exercise and Active Living, Victoria University, Footscray, VIC, AustraliaBasic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Melbourne, VIC, AustraliaVascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Clayton, VIC, AustraliaMetabolic and Vascular Physiology Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, AustraliaDiabetes & Metabolism Division, Garvan Institute of Medical Research, NSW, AustraliaCellular and Molecular Metabolism Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, Australia; Diabetes & Metabolism Division, Garvan Institute of Medical Research, NSW, Australia; Corresponding author. Division of Diabetes & Metabolism, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, NSW, 2010, Australia.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. Author Video: Author Video Watch what authors say about their articles Keywords: Glucose metabolism, Enzyme activity, Insulin sensitivityhttp://www.sciencedirect.com/science/article/pii/S2212877816301338 |
| spellingShingle | Robert S. Lee-Young Nolan J. Hoffman Kate T. Murphy Darren C. Henstridge Dorit Samocha-Bonet Andrew L. Siebel Peter Iliades Borivoj Zivanovic Yet H. Hong Timothy D. Colgan Michael J. Kraakman Clinton R. Bruce Paul Gregorevic Glenn K. McConell Gordon S. Lynch Grant R. Drummond Bronwyn A. Kingwell Jerry R. Greenfield Mark A. Febbraio Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle Molecular Metabolism |
| title | Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle |
| title_full | Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle |
| title_fullStr | Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle |
| title_full_unstemmed | Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle |
| title_short | Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle |
| title_sort | glucose 6 phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle |
| url | http://www.sciencedirect.com/science/article/pii/S2212877816301338 |
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