Gender Dimorphic Relationships of Adiposity, Fitness, and Physical Activity with Indices of Skeletal Muscle and Hepatic Insulin Sensitivity in Healthy Older Subjects.

Context: African-American women (AAW) have an increased risk of developing type 2 diabetes compared with Caucasian women (CW). Lower insulin sensitivity has been reported in AAW, but the reasons for this racial difference and the contributions of liver versus skeletal muscle are incompletely understood. Objective: We tested the hypothesis that young, nonobese AAW manifest lower insulin sensitivity specific to skeletal muscle, not liver, and is accompanied by lower skeletal muscle mitochondrial oxidative capacity. Participants and Main Outcome Measures: Twenty-two nonobese (body mass index 22.7 ± 3.1 kg/m2) AAW and 22 matched CW (body mass index 22.7 ± 3.1 kg/m2) underwent characterization of body composition, objectively assessed habitual physical activity, and insulin sensitivity with euglycemic clamps and stable-isotope tracers. Skeletal muscle biopsies were performed for lipid content, fiber typing, and mitochondrial measurements. Results: Peripheral insulin sensitivity was 26% lower in AAW (P < .01), but hepatic insulin sensitivity was similar between groups. Physical activity levels were similar between groups. Lower insulin sensitivity in AAW was not explained by total or central adiposity. Skeletal muscle triglyceride content was similar, but mitochondrial content was lower in AAW. Mitochondrial respiration was 24% lower in AAW and correlated with skeletal muscle insulin sensitivity (r = 0.33, P < .05). Conclusion: When compared with CW, AAW have similar hepatic insulin sensitivity but a muscle phenotype characterized by both lower insulin sensitivity and lower mitochondrial oxidative capacity. These observations occur in the absence of obesity and are not explained by physical activity. The only factor associated with lower insulin sensitivity in AAW was mitochondrial oxidative capacity. Because exercise training improves both mitochondrial capacity and insulin sensitivity, we suggest that it may be of particular benefit as a strategy for diabetes prevention in AAW.

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Faculty Opinions recommendation of Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717147862.792403066 ◽

2012 ◽

Author(s):

Ajay Chawla

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Ppar Gamma ◽

Hepatic Insulin Sensitivity ◽

Antidiabetic Effects

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Interactions between insulin and exercise

Biochemical Journal ◽

10.1042/bcj20210185 ◽

2021 ◽

Vol 478 (21) ◽

pp. 3827-3846

Author(s):

Erik A. Richter ◽

Lykke Sylow ◽

Mark Hargreaves

Keyword(s):

Physical Activity ◽

Skeletal Muscle ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Insulin Action ◽

Regular Exercise ◽

Fuel Storage ◽

Storage Effects ◽

Glucose Storage ◽

Glycogen Stores

The interaction between insulin and exercise is an example of balancing and modifying the effects of two opposing metabolic regulatory forces under varying conditions. While insulin is secreted after food intake and is the primary hormone increasing glucose storage as glycogen and fatty acid storage as triglycerides, exercise is a condition where fuel stores need to be mobilized and oxidized. Thus, during physical activity the fuel storage effects of insulin need to be suppressed. This is done primarily by inhibiting insulin secretion during exercise as well as activating local and systemic fuel mobilizing processes. In contrast, following exercise there is a need for refilling the fuel depots mobilized during exercise, particularly the glycogen stores in muscle. This process is facilitated by an increase in insulin sensitivity of the muscles previously engaged in physical activity which directs glucose to glycogen resynthesis. In physically trained individuals, insulin sensitivity is also higher than in untrained individuals due to adaptations in the vasculature, skeletal muscle and adipose tissue. In this paper, we review the interactions between insulin and exercise during and after exercise, as well as the effects of regular exercise training on insulin action.

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Influence of Exercise Training on Skeletal Muscle Insulin Resistance in Aging: Spotlight on Muscle Ceramides

International Journal of Molecular Sciences ◽

10.3390/ijms21041514 ◽

2020 ◽

Vol 21 (4) ◽

pp. 1514 ◽

Cited By ~ 4

Author(s):

Paul T. Reidy ◽

Ziad S. Mahmassani ◽

Alec I. McKenzie ◽

Jonathan J. Petrocelli ◽

Scott A. Summers ◽

...

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Insulin Sensitivity ◽

Muscle Contraction ◽

Contractile Activity ◽

Skeletal Muscle Insulin Resistance ◽

Ceramide Content ◽

Subcellular Compartmentalization ◽

Skeletal Muscle Insulin Sensitivity

Intramuscular lipid accumulation has been associated with insulin resistance (IR), aging, diabetes, dyslipidemia, and obesity. A substantial body of evidence has implicated ceramides, a sphingolipid intermediate, as potent antagonists of insulin action that drive insulin resistance. Indeed, genetic mouse studies that lower ceramides are potently insulin sensitizing. Surprisingly less is known about how physical activity (skeletal muscle contraction) regulates ceramides, especially in light that muscle contraction regulates insulin sensitivity. The purpose of this review is to critically evaluate studies (rodent and human) concerning the relationship between skeletal muscle ceramides and IR in response to increased physical activity. Our review of the literature indicates that chronic exercise reduces ceramide levels in individuals with obesity, diabetes, or hyperlipidemia. However, metabolically healthy individuals engaged in increased physical activity can improve insulin sensitivity independent of changes in skeletal muscle ceramide content. Herein we discuss these studies and provide context regarding the technical limitations (e.g., difficulty assessing the myriad ceramide species, the challenge of obtaining information on subcellular compartmentalization, and the paucity of flux measurements) and a lack of mechanistic studies that prevent a more sophisticated assessment of the ceramide pathway during increased contractile activity that lead to divergences in skeletal muscle insulin sensitivity.

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Lipid in skeletal muscle myotubes is associated to the donors' insulin sensitivity and physical activity phenotypes

Obesity ◽

10.1002/oby.20556 ◽

2013 ◽

Vol 22 (2) ◽

pp. 426-434 ◽

Cited By ~ 13

Author(s):

Sudip Bajpeyi ◽

Cassandra K. Myrland ◽

Jeffrey D. Covington ◽

Diana Obanda ◽

William T. Cefalu ◽

...

Keyword(s):

Physical Activity ◽

Skeletal Muscle ◽

Insulin Sensitivity

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Changes Induced by Physical Activity and Weight Loss in the Morphology of Intermyofibrillar Mitochondria in Obese Men and Women

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-0002 ◽

2006 ◽

Vol 91 (8) ◽

pp. 3224-3227 ◽

Cited By ~ 77

Author(s):

Frederico G. S. Toledo ◽

Simon Watkins ◽

David E. Kelley

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Weight Loss ◽

Insulin Sensitivity ◽

Lifestyle Modification ◽

Vastus Lateralis ◽

Vastus Lateralis Muscle ◽

Mitochondrial Content ◽

The Mean

Abstract Context: In obesity, skeletal muscle insulin resistance may be associated with smaller mitochondria. Objective: Our objective was to examine the effect of a lifestyle-modification intervention on the content and morphology of skeletal muscle mitochondria and its relationship to insulin sensitivity in obese, insulin-resistant subjects. Design: In this prospective interventional study, intermyofibrillar mitochondrial content and size were quantified by transmission electron microscopy with quantitative morphometric analysis of biopsy samples from vastus lateralis muscle. Systemic insulin sensitivity was measured with euglycemic hyperinsulinemic clamps. Setting: The study took place at a university-based clinical research center. Participants: Eleven sedentary, overweight/obese volunteers without diabetes participated in the study. Intervention: Intervention included 16 wk of aerobic training with dietary restriction of 500-1000 kcal/d. Main Outcome Measures: We assessed changes in mitochondrial content and size and changes in insulin sensitivity. Results: The percentage of myofiber volume occupied by mitochondria significantly increased from 3.70 ± 0.31 to 4.87 ± 0.33% after intervention (P = 0.01). The mean individual increase was 42.5 ± 18.1%. There was also a change in the mean cross-sectional mitochondrial area, increasing from a baseline of 0.078 ± 0.007 to 0.091 ± 0.007 μm2 (P < 0.01), a mean increase of 19.2 ± 6.1% per subject. These changes in mitochondrial size and content highly correlated with improvements in insulin resistance (r = 0.68 and 0.72, respectively; P = 0.01). Conclusions: A combined intervention of weight loss and physical activity in previously sedentary obese adults is associated with enlargement of mitochondria and an increase in the mitochondrial content in skeletal muscle. These findings indicate that in obesity with insulin resistance, ultrastructural mitochondrial plasticity is substantially retained and, importantly, that changes in the morphology of mitochondria are associated with improvements in insulin resistance.

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Adipose Depots, Not Disease-related Factors, Account for Skeletal Muscle Insulin Sensitivity in Established and Treated Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.140224 ◽

2014 ◽

Vol 41 (10) ◽

pp. 1974-1979 ◽

Cited By ~ 19

Author(s):

Hiba AbouAssi ◽

K. Noelle Tune ◽

Brian Gilmore ◽

Lori A. Bateman ◽

Gary McDaniel ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Physical Activity ◽

Skeletal Muscle ◽

Body Composition ◽

Insulin Sensitivity ◽

Systemic Inflammation ◽

Geometric Mean ◽

Related Factors ◽

Intravenous Glucose ◽

Skeletal Muscle Insulin Sensitivity

Objective.In prior reports, individuals with rheumatoid arthritis (RA) exhibited increased insulin resistance. However, those studies were limited by either suboptimal assessment methods for insulin sensitivity or a failure to account for important determinants such as adiposity and lack of physical activity. Our objectives were to carefully assess, compare, and determine predictors of skeletal muscle insulin sensitivity in RA, accounting for adiposity and physical activity.Methods.Thirty-nine individuals with established (seropositive or erosions) and treated RA and 39 controls matched for age, sex, race, body mass index, and physical activity underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity. Inflammation, body composition, and physical activity were assessed with systemic cytokine measurements, computed tomography scans, and accelerometry, respectively. Exclusions were diabetes, cardiovascular disease, medication changes within 3 months, and prednisone use over 5 mg/day. This investigation was powered to detect a clinically significant, moderate effect size for insulin sensitivity difference.Results.Despite elevated systemic inflammation [interleukin (IL)-6, IL-18, tumor necrosis factor-α; p < 0.05 for all], persons with RA were not less insulin sensitive [SIgeometric mean (SD): RA 4.0 (2.4) vs control 4.9 (2.1)*10−5min−1/(pmol/l); p = 0.39]. Except for visceral adiposity being slightly greater in controls (p = 0.03), there were no differences in body composition or physical activity. Lower insulin sensitivity was independently associated with increased abdominal and thigh adiposity, but not with cytokines, disease activity, duration, disability, or disease-modifying medication use.Conclusion.In established and treated RA, traditional risk factors, specifically excess adiposity, play more of a role in predicting skeletal muscle insulin sensitivity than do systemic inflammation or other disease-related factors.

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TheFOXO3Ars2802292 G-Allele Associates with Improved Peripheral and Hepatic Insulin Sensitivity and Increased Skeletal Muscle-FOXO3AmRNA Expression in Twins

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-0881 ◽

2011 ◽

Vol 96 (1) ◽

pp. E119-E124 ◽

Cited By ~ 28

Author(s):

Karina Banasik ◽

Rasmus Ribel-Madsen ◽

Anette P. Gjesing ◽

Lise Wegner ◽

Åsa Andersson ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Hepatic Insulin Sensitivity

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Macrophage PPARγ is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones

Journal of Clinical Investigation ◽

10.1172/jci31561 ◽

2007 ◽

Vol 117 (6) ◽

pp. 1658-1669 ◽

Cited By ~ 358

Author(s):

Andrea L. Hevener ◽

Jerrold M. Olefsky ◽

Donna Reichart ◽

M.T. Audrey Nguyen ◽

Gautam Bandyopadyhay ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Hepatic Insulin Sensitivity ◽

Antidiabetic Effects

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Body composition is distinctly altered in Turner syndrome: relations to glucose metabolism, circulating adipokines, and endothelial adhesion molecules

Acta Endocrinologica ◽

10.1530/eje.1.02267 ◽

2006 ◽

Vol 155 (4) ◽

pp. 583-592 ◽

Cited By ~ 63

Author(s):

Claus Højbjerg Gravholt ◽

Britta Eilersen Hjerrild ◽

Leif Mosekilde ◽

Troels Krarup Hansen ◽

Lars Melholt Rasmussen ◽

...

Keyword(s):

Physical Activity ◽

Skeletal Muscle ◽

Body Composition ◽

Insulin Sensitivity ◽

Muscle Mass ◽

Regression Models ◽

Skeletal Muscle Mass ◽

Cell Adhesion Molecule ◽

Linear Regression Models ◽

Multiple Linear Regression Models

Background: Body composition in Turner syndrome (TS) is altered with final height of TS decreased; anthropometry and bone mass distinctly changed. Aim: To describe total and regional distribution of fat and muscle mass in TS and the relation to measures of glucose metabolism, sex hormones, IGFs, and markers of inflammation and vascular function. Material and methods: Fifty-four women with TS (mean age, 42.5 ± 9.7 years) and an age-matched group of controls (n = 55) were examined by dual-energy X-ray absorptiometry scans with determination of regional body composition and estimation of visceral fat and skeletal muscle mass. We determined maximal oxygen uptake and assessed physical activity using a questionnaire. We measured serum adiponectin, ghrelin, IGF-I, IGF-binding protein-3 (IGFBP-3), estradiol, testosterone, sex hormone-binding globulin (SHBG), insulin, glucose, cytokines, vascular cell adhesion molecule-I, and intercellular cell adhesion molecule-I. Insulin sensitivity was estimated. Multiple linear regression models were used to examine the relationships between variables. Results: TS had lower total lean body mass (LBM), while body mass index (BMI) and total fat mass (FM) were increased. We found increased visceral FM, and decreased trunk LBM, appendicular LBM, and skeletal muscle mass. VO2max and physical activity were significantly lower in TS, as were most hormone levels, except increased leptin. In multiple linear regression models, status (i.e. TS or control) was a consistent contributing variable. Conclusion: Profound changes are present in body composition in TS, with increased FM, and decreased skeletal muscle mass. Circulating hormones, VO2max, and insulin sensitivity influence body composition. The accumulation of visceral fat would predict a higher risk of development of the insulin resistance syndrome.

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