Sex and Race Contribute to Variation in Mitochondrial Function and Insulin Sensitivity

Overview

Journal Physiol Rep

Specialty Physiology

Date 2021 Oct 4

PMID 34605220

Citations 4

Authors

Gordon Fisher

Jeannie Tay

Jonathan L Warren

W Timothy Garvey

Ceren Yarar-Fisher

Barbara A Gower

Affiliations

Soon will be listed here.

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 H O 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 m , were assessed for insulin sensitivity (SI ) using a euglycemic clamp at 120 mU/m /min, muscle mitochondrial function using high-resolution respirometry, H O emission using amplex red, and % myofiber composition.

Results: SI 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 H O production did not differ with race. Mitochondrial function was positively associated with insulin sensitivity in women but not men. Statistical adjustment for mitochondrial function, H O production, or fiber composition did not eliminate the race difference in SI .

Conclusion: Neither mitochondrial respiratory rates, coupling efficiency, myofiber composition, nor mitochondrial reactive oxygen species production explained lower SI 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.

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

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References

Gallagher D, Kuznia P, Heshka S, Albu J, Heymsfield S, Goodpaster B . Adipose tissue in muscle: a novel depot similar in size to visceral adipose tissue. Am J Clin Nutr. 2005; 81(4):903-10. PMC: 1482784. DOI: 10.1093/ajcn/81.4.903. View

Kriketos A, Pan D, Lillioja S, Cooney G, Baur L, Milner M . Interrelationships between muscle morphology, insulin action, and adiposity. Am J Physiol. 1996; 270(6 Pt 2):R1332-9. DOI: 10.1152/ajpregu.1996.270.6.R1332. View

Jakicic J, Wing R . Differences in resting energy expenditure in African-American vs Caucasian overweight females. Int J Obes Relat Metab Disord. 1998; 22(3):236-42. DOI: 10.1038/sj.ijo.0800575. View

Stuart C, McCurry M, Marino A, South M, Howell M, Layne A . Slow-twitch fiber proportion in skeletal muscle correlates with insulin responsiveness. J Clin Endocrinol Metab. 2013; 98(5):2027-36. PMC: 3644602. DOI: 10.1210/jc.2012-3876. View

Beebe-Dimmer J, Ruterbusch J, Cooney K, Bolton A, Schwartz K, Schwartz A . Racial differences in patterns of treatment among men diagnosed with de novo advanced prostate cancer: A SEER-Medicare investigation. Cancer Med. 2019; 8(6):3325-3335. PMC: 6558501. DOI: 10.1002/cam4.2092. View

Befroy D, Petersen K, Dufour S, Mason G, de Graaf R, Rothman D . Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients. Diabetes. 2007; 56(5):1376-81. PMC: 2995532. DOI: 10.2337/db06-0783. View

Mishmar D, Ruiz-Pesini E, Golik P, Macaulay V, Clark A, Hosseini S . Natural selection shaped regional mtDNA variation in humans. Proc Natl Acad Sci U S A. 2003; 100(1):171-6. PMC: 140917. DOI: 10.1073/pnas.0136972100. View

Paula F, Pimenta W, Saad M, Paccola G, Piccinato C, Foss M . Sex-related differences in peripheral glucose metabolism in normal subjects. Diabete Metab. 1990; 16(3):234-9. View

Brunelli E, Domanico F, La Russa D, Pellegrino D . Sex differences in oxidative stress biomarkers. Curr Drug Targets. 2014; 15(8):811-5. DOI: 10.2174/1389450115666140624112317. View

10.

Wild S, Roglic G, Green A, Sicree R, King H . Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004; 27(5):1047-53. DOI: 10.2337/diacare.27.5.1047. View

11.

Hasson B, Apovian C, Istfan N . Racial/Ethnic Differences in Insulin Resistance and Beta Cell Function: Relationship to Racial Disparities in Type 2 Diabetes among African Americans versus Caucasians. Curr Obes Rep. 2015; 4(2):241-9. DOI: 10.1007/s13679-015-0150-2. View

12.

Montero D, Madsen K, Meinild-Lundby A, Edin F, Lundby C . Sexual dimorphism of substrate utilization: Differences in skeletal muscle mitochondrial volume density and function. Exp Physiol. 2018; 103(6):851-859. DOI: 10.1113/EP087007. View

13.

Fridlyand L, Philipson L . Cold climate genes and the prevalence of type 2 diabetes mellitus. Med Hypotheses. 2006; 67(5):1034-41. DOI: 10.1016/j.mehy.2006.04.057. View

14.

OBrien T, Flanders W, DECOUFLE P, Boyle C, DeStefano F, Teutsch S . Are racial differences in the prevalence of diabetes in adults explained by differences in obesity?. JAMA. 1989; 262(11):1485-8. View

15.

Privette J, Hickner R, Macdonald K, Pories W, Barakat H . Fatty acid oxidation by skeletal muscle homogenates from morbidly obese black and white American women. Metabolism. 2003; 52(6):735-8. DOI: 10.1016/s0026-0495(03)00034-9. View

16.

Fisher G, Windham S, Griffin P, Warren J, Gower B, Hunter G . Associations of human skeletal muscle fiber type and insulin sensitivity, blood lipids, and vascular hemodynamics in a cohort of premenopausal women. Eur J Appl Physiol. 2017; 117(7):1413-1422. PMC: 5963254. DOI: 10.1007/s00421-017-3634-9. View

17.

DeLany J, Dube J, Standley R, Distefano G, Goodpaster B, Stefanovic-Racic M . Racial differences in peripheral insulin sensitivity and mitochondrial capacity in the absence of obesity. J Clin Endocrinol Metab. 2014; 99(11):4307-14. PMC: 4223429. DOI: 10.1210/jc.2014-2512. View

18.

Hunter G, McCarthy J, Bamman M, Larson-Meyer D, Fisher G, Newcomer B . Exercise economy in African American and European American women. Eur J Appl Physiol. 2011; 111(8):1863-9. PMC: 3137679. DOI: 10.1007/s00421-010-1816-9. View

19.

Hancock C, Han D, Chen M, Terada S, Yasuda T, Wright D . High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Proc Natl Acad Sci U S A. 2008; 105(22):7815-20. PMC: 2409421. DOI: 10.1073/pnas.0802057105. View

20.

Egede L, Mueller M, Echols C, Gebregziabher M . Longitudinal differences in glycemic control by race/ethnicity among veterans with type 2 diabetes. Med Care. 2010; 48(6):527-33. DOI: 10.1097/MLR.0b013e3181d558dc. View