Single‐leg exercise training augments in vivo skeletal muscle oxidative flux and vascular content and function in adults with type 2 diabetes
- 5 March 2021
- journal article
- research article
- Published by Wiley in Journal Of Physiology-London
- Vol. 600 (4), 963-978
- https://doi.org/10.1113/jp280603
Abstract
Key points People with type 2 diabetes (T2D) have impaired skeletal muscle oxidative flux due to limited oxygen delivery. In the current study, this impairment in oxidative flux in people with T2D was abrogated with a single‐leg exercise training protocol. Additionally, single‐leg exercise training increased skeletal muscle CD31 content, calf blood flow, and state 4 mitochondrial respiration in all participants. Abstract Cardiorespiratory fitness is impaired in type 2 diabetes (T2D) conferring significant cardiovascular risk in this population; interventions are needed. Previously, we reported that a T2D‐associated decrement in skeletal muscle oxidative flux is ameliorated with acute use of supplemental oxygen, suggesting that skeletal muscle oxygenation is rate limiting to in vivo mitochondrial oxidative flux during exercise in T2D. We hypothesized that single‐leg exercise training (SLET) would improve the T2D‐specific impairment in in vivo mitochondrial oxidative flux during exercise. Adults with (n = 19) and without T2D (n = 22) with similar body mass indexes and levels of physical activity participated in two weeks of SLET. Following SLET, in vivo oxidative flux measured by 31P‐MRS increased in participants with T2D, but not people without T2D, measured by the increase in initial phosphocreatine synthesis (P = 0.0455 for the group x exercise interaction) and maximum rate of oxidative ATP synthesis (P = 0.0286 for the interaction). Additionally, oxidative phosphorylation increased in all participants with SLET (P = 0.0209). After SLET, there was no effect of supplemental oxygen on any of the in vivo oxidative flux measurements in either group (P>0.02), consistent with resolution of the T2D‐associated oxygen limitation previously observed at baseline in subjects with T2D. State 4 mitochondrial respiration also improved in muscle fibers ex vivo. Skeletal muscle vasculature content and calf blood flow increased in all participants with SLET (PP = 0.0461). SLET resolves the T2D‐associated impairment of skeletal muscle in vivo mitochondrial oxidative flux potentially through improved effective blood flow/oxygen delivery. This article is protected by copyright. All rights reservedFunding Information
- Doris Duke Charitable Foundation (2015212)
- National Institute of Diabetes and Digestive and Kidney Diseases (K23‐DK‐107871)
- U.S. Department of Veterans Affairs (BX002046)
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