Sex and race contribute to variation in mitochondrial function and insulin sensitivity

Physiol Rep. 2021 Oct;9(19):e15049. doi: 10.14814/phy2.15049.

Abstract

Objective: Insulin sensitivity is lower in African American (AA) versus Caucasian American (CA). We tested the hypothesis that lower insulin sensitivity in AA could be explained by mitochondrial respiratory rates, coupling efficiency, myofiber composition, or H2 O2 emission. A secondary aim was to determine whether sex affected the results.

Methods: AA and CA men and women, 19-45 years, BMI 17-43 kg m2 , were assessed for insulin sensitivity (SIClamp ) using a euglycemic clamp at 120 mU/m2 /min, muscle mitochondrial function using high-resolution respirometry, H2 O2 emission using amplex red, and % myofiber composition.

Results: SIClamp was greater in CA (p < 0.01) and women (p < 0.01). Proportion of type I myofibers was lower in AA (p < 0.01). Mitochondrial respiratory rates, coupling efficiency, and H2 O2 production did not differ with race. Mitochondrial function was positively associated with insulin sensitivity in women but not men. Statistical adjustment for mitochondrial function, H2 O2 production, or fiber composition did not eliminate the race difference in SIClamp .

Conclusion: Neither mitochondrial respiratory rates, coupling efficiency, myofiber composition, nor mitochondrial reactive oxygen species production explained lower SIClamp in AA compared to CA. The source of lower insulin sensitivity in AA may be due to other aspects of skeletal muscle that have yet to be identified.

Trial registration: ClinicalTrials.gov NCT03043235.

Keywords: insulin sensitivity; mitochondrial function; race; reactive oxygen species; sex.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Cross-Sectional Studies
  • Female
  • Glucose Clamp Technique
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Insulin / pharmacology*
  • Insulin Resistance / physiology*
  • Male
  • Middle Aged
  • Mitochondria, Muscle / drug effects
  • Mitochondria, Muscle / metabolism*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Sex Factors
  • Young Adult

Substances

  • Hypoglycemic Agents
  • Insulin
  • Reactive Oxygen Species

Associated data

  • ClinicalTrials.gov/NCT03043235