Single-leg exercise training augments in vivo skeletal muscle oxidative flux and vascular content and function in adults with type 2 diabetes

Rebecca L. Scalzo, Irene E. Schauer, Deirdre Rafferty, Leslie A. Knaub, Nina Kvaratskhelia, Taro Kaelix Johnson, Gregory B. Pott, Layla A. Abushamat, Mary O. Whipple, Amy G. Huebschmann, Melanie Cree-Green, Jane E.B. Reusch, Judith G. Regensteiner

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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 × 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 fibres ex vivo. Skeletal muscle vasculature content and calf blood flow increased in all participants with SLET (P < 0.0040); oxygen extraction in the calf increased only in T2D (P = 0.0461). SLET resolves the T2D-associated impairment of skeletal muscle in vivo mitochondrial oxidative flux potentially through improved effective blood flow/oxygen delivery.

Original languageEnglish (US)
Pages (from-to)963-978
Number of pages16
JournalJournal of Physiology
Issue number4
StatePublished - Feb 15 2022
Externally publishedYes

Bibliographical note

Funding Information:
This study was funded by the following: the Eugene Armstrong Family Foundation, an American Diabetes Association Clinical Research Grant (1‐12‐CT‐64 to J.G.R. and J.E.B.R.), a Veterans Administration Career Development Award (BX004533 to R.L.S.), the National Institutes of Health (NIH)/National Center for Research Resources (T32‐DK‐063687 and K23‐DK‐107871 to MC‐G), NIH Building Interdisciplinary Research Careers in Women's Health (2K12‐HD‐057022 IES and MC‐G), the Doris Duke Foundation (2015212 to MC‐G), the Denver Research Institute pilot (IES), the Eastern Colorado Geriatric Research, Education, and Clinical Center (IES), a Veterans Administration Merit Award (CVP BX002046 to JEBR), the NIH/National Center for Advancing Translational Sciences (Colorado CTSA UL1‐TR‐001082) and Magnet NIH (1S10‐OD‐018435).

Publisher Copyright:
© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society


  • blood flow
  • diabetes
  • exercise
  • skeletal muscle
  • Oxygen Consumption/physiology
  • Oxidative Stress
  • Humans
  • Adult
  • Diabetes Mellitus, Type 2/metabolism
  • Exercise/physiology
  • Leg/physiology
  • Muscle, Skeletal/physiology

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Journal Article
  • Research Support, N.I.H., Extramural


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