Ascorbic acid supplementation improves skeletal muscle oxidative stress and insulin sensitivity in people with type 2 diabetes: findings of a randomized controlled study

Mason, Shaun A., Della Gatta, Paul A., Snow, Rod J., Russell, Aaron P. and Wadley, Glenn D. 2016, Ascorbic acid supplementation improves skeletal muscle oxidative stress and insulin sensitivity in people with type 2 diabetes: findings of a randomized controlled study, Free radical biology and medicine, vol. 93, pp. 227-238, doi: 10.1016/j.freeradbiomed.2016.01.006.

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Title Ascorbic acid supplementation improves skeletal muscle oxidative stress and insulin sensitivity in people with type 2 diabetes: findings of a randomized controlled study
Author(s) Mason, Shaun A.ORCID iD for Mason, Shaun A. orcid.org/0000-0002-6138-2239
Della Gatta, Paul A.ORCID iD for Della Gatta, Paul A. orcid.org/0000-0003-2231-8370
Snow, Rod J.ORCID iD for Snow, Rod J. orcid.org/0000-0002-4796-6916
Russell, Aaron P.ORCID iD for Russell, Aaron P. orcid.org/0000-0002-7323-9501
Wadley, Glenn D.ORCID iD for Wadley, Glenn D. orcid.org/0000-0002-6617-4359
Journal name Free radical biology and medicine
Volume number 93
Start page 227
End page 238
Total pages 12
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2016-04
ISSN 1873-4596
Keyword(s) Ascorbic acid
Oxidative stress
Skeletal muscle
Type 2 diabetes
Summary AIM/HYPOTHESIS: Skeletal muscle insulin resistance and oxidative stress are characteristic metabolic disturbances in people with type 2 diabetes. Studies in insulin resistant rodents show an improvement in skeletal muscle insulin sensitivity and oxidative stress following antioxidant supplementation. We therefore investigated the potential ameliorative effects of antioxidant ascorbic acid (AA) supplementation on skeletal muscle insulin sensitivity and oxidative stress in people with type 2 diabetes. METHODS: Participants with stable glucose control commenced a randomized cross-over study involving four months of AA (2×500mg/day) or placebo supplementation. Insulin sensitivity was assessed using a hyperinsulinaemic, euglycaemic clamp coupled with infusion of 6,6-D2 glucose. Muscle biopsies were measured for AA concentration and oxidative stress markers that included basal measures (2',7'-dichlorofluorescin [DCFH] oxidation, ratio of reduced-to-oxidized glutathione [GSH/GSSG] and F2-Isoprostanes) and insulin-stimulated measures (DCFH oxidation). Antioxidant concentrations, citrate synthase activity and protein abundances of sodium-dependent vitamin C transporter 2 (SVCT2), total Akt and phosphorylated Akt (ser473) were also measured in muscle samples. RESULTS: AA supplementation significantly increased insulin-mediated glucose disposal (delta rate of glucose disappearance; ∆Rd) (p=0.009), peripheral insulin-sensitivity index (p=0.046), skeletal muscle AA concentration (p=0.017) and muscle SVCT2 protein expression (p=0.008); but significantly decreased skeletal muscle DCFH oxidation during hyperinsulinaemia (p=0.007) when compared with placebo. Total superoxide dismutase activity was also lower following AA supplementation when compared with placebo (p=0.006). Basal oxidative stress markers, citrate synthase activity, endogenous glucose production, HbA1C and muscle Akt expression were not significantly altered by AA supplementation. CONCLUSIONS/INTERPRETATION: In summary, oral AA supplementation ameliorates skeletal muscle oxidative stress during hyperinsulinaemia and improves insulin-mediated glucose disposal in people with type 2 diabetes. Findings implicate AA supplementation as a potentially inexpensive, convenient, and effective adjunct therapy in the treatment of insulin resistance in people with type 2 diabetes.
Language eng
DOI 10.1016/j.freeradbiomed.2016.01.006
Field of Research 110602 Exercise Physiology
0304 Medicinal And Biomolecular Chemistry
0601 Biochemistry And Cell Biology
Socio Economic Objective 920104 Diabetes
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Elsevier
Persistent URL http://hdl.handle.net/10536/DRO/DU:30081566

Document type: Journal Article
Collections: Faculty of Health
School of Exercise and Nutrition Sciences
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