Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes

Malin, Steven K.; Haus, Jacob M.; Solomon, Thomas P. J.; Blaszczak, Alecia; Kashyap, Sangeeta R.; Kirwan, John P.

doi:10.1152/ajpendo.00441.2013

Cited by 89Diabetes, Cardiovascular Risks, and LipoproteinsPhysical Activity and HealthCardiovascular and exercise physiology

Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes

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Malin, Steven K., Haus, Jacob M., Solomon, Thomas P. J., Blaszczak, Alecia, Kashyap, Sangeeta R., Kirwan, John P.·2013·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.00441.2013PMC PMC3840211

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Abstract

Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG + IGT is unknown. Twenty-four older (66.7 ± 0.8 yr) obese (34.2 ± 0.9 kg/m(2)) adults were categorized as IFG (n = 8), IGT (n = 8), or IFG + IGT (n = 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at ∼85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m(2)·min(-1)) with [6,6-(2)H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG + IGT (P < 0.05). Exercise reduced glucose iAUCOGTT in IGT only (P < 0.05), and the decrease in glucose iAUCOGTT was inversely correlated with the increase in peripheral but not hepatic insulin sensitivity (P < 0.01). Increased clamp-derived peripheral insulin sensitivity was also correlated with enhanced metabolic flexibility, reduced fasting RQ, and higher nonoxidative glucose disposal (P < 0.05). Adults with IFG + IGT had smaller gains in clamp-derived peripheral insulin sensitivity and metabolic flexibility, which was related to blunted improvements in postprandial glucose. Additional work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training.

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Improving glycogen synthesis strongly influences exercise-induced skeletal muscle insulin sensitivity.
“improving glycogen synthesis strongly influences exercise-induced skeletal muscle insulin sensitivity”
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Authors: Malin, S. K., Haus, J. M., Solomon, T. P. J., Blaszczak, A., Kashyap, S. R., & Kirwan, J. P.
Affiliations: Cleveland Clinic (US)
University of Illinois Chicago (US)
University of Copenhagen (DK)
Corresponding author: Kirwan, John P.
ORCID: Malin, Steven K.
Haus, Jacob M.
Solomon, Thomas P. J.
Blaszczak, Alecia
Kashyap, Sangeeta R.
Kirwan, John P.
Venue: American Journal of Physiology-Endocrinology and Metabolism
Publisher: American Physiological Society
Published: 2013-11-15
Volume: 305
Issue: 10
Pages: E1292-E1298
ISSN: 0193-1849 (ISSN-L)
1522-1555
DOI: 10.1152/ajpendo.00441.2013
PMC: PMC3840211
OpenAlex: W2162428492
Cited by: 89
References: 43
Citations by year: 2026: 5 · 2025: 3 · 2024: 10 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 8 · 2019: 8 · 2018: 10 · 2017: 9 · 2016: 11 · 2015: 7 · 2014: 4
FWCI: 5.77
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Funders: Cleveland Clinic
National Institutes of Health (UL1TR000439)
National Institute on Aging (R01AG012834, R01AG12834)
National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007319)
National Center for Research Resources (UL1RR024989)
National Center for Advancing Translational Sciences
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Physiology › Physical Activity and Health
Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
Keywords: insulin sensitivity, metabolic flexibility, exercise training, insulin resistance, impaired fasting glucose, impaired glucose tolerance, obesity, hepatic insulin sensitivity, peripheral insulin sensitivity, respiratory quotient, nonoxidative glucose disposal, postprandial blood glucose, older adults, chronic hyperglycemia
MeSH terms: Aged, Blood Glucose, Fasting, Female, Glucose Tolerance Test, Humans, Insulin Resistance, Male, Middle Aged, Obesity, Phenotype, Physical Education and Training, Prediabetic State, Exercise, Glucose Intolerance

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Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes

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