Cited by 1,179Diabetes, Cardiovascular Risks, and LipoproteinsAdipose Tissue and MetabolismMetabolism, Diabetes, and Cancer

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Skeletal Muscle Triglyceride Levels Are Inversely Related to Insulin Action

Pan, D A, Lillioja, S, Kriketos, A D, Milner, M R, Baur, L A, Bogardus, C, Jenkins, A B, Storlien, L H·1997·Diabetes

DOI 10.2337/diab.46.6.983

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Abstract

In animal studies, increased amounts of triglyceride associated with skeletal muscle (mTG) correlate with reduced skeletal muscle and whole body insulin action. The aim of this study was to test this relationship in humans. Subjects were 38 nondiabetic male Pima Indians (mean age 28 ± 1 years). Insulin sensitivity at physiological (M) and supraphysiological (MZ) insulin levels was assessed by the euglycemic clamp. Lipid and carbohydrate oxidation were determined by indirect calorimetry before and during insulin administration. mTG was determined in vastus lateralis muscles obtained by percutaneous biopsy. Percentage of body fat (mean 29 ± 1%, range 14–44%) was measured by underwater weighing. In simple regressions, negative relationships were found between mTG (mean 5.4 ± 0.3 μmol/g, range 1.3–1.9 μmol/g) and log10M (r = −0.53, P ≤ 0.001), MZ (r = −0.44, P = 0.006), and nonoxidative glucose disposal (r = −0.48 and −0.47 at physiological and supraphysiological insulin levels, respectively, both P = 0.005) but not glucose or lipid oxidation. mTG was not related to any measure of adiposity. In multiple regressions, measures of insulin resistance (log10M, MZ, log10[fasting insulin]) were significantly related to mTG independent of all measures of obesity (percentage of body fat, BMI, waist-to-thigh ratio). In turn, all measures of obesity were related to the insulin resistance measures independent of mTG. The obesity measures and mTG accounted for similar proportions of the variance in insulin resistance in these relationships. The results suggest that in this human population, as in animal models, skeletal muscle insulin sensitivity is strongly influenced by local supplies of triglycerides, as well as by remote depots and circulating lipids. The mechanism(s) underlying the relationship between mTG and insulin action on skeletal muscle glycogen synthesis may be central to an understanding of insulin resistance.

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Background
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Authors: Pan, D. A., Lillioja, S., Kriketos, A. D., Milner, M. R., Baur, L. A., Bogardus, C., Jenkins, A. B., & Storlien, L. H.
Affiliations: University of Wollongong (AU)
National Institute of Diabetes and Digestive and Kidney Diseases (US)
Royal Prince Alfred Hospital (AU)
ORCID: Pan, D A
Lillioja, S
Baur, L A
Bogardus, C
Jenkins, A B
Venue: Diabetes
Publisher: American Diabetes Association
Published: 1997-06-01
Volume: 46
Issue: 6
Pages: 983-988
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diab.46.6.983
OpenAlex: W2134604231
Cited by: 1,179
References: 37
Citations by year: 2026: 2 · 2025: 17 · 2024: 14 · 2023: 26 · 2022: 23 · 2021: 28 · 2020: 25 · 2019: 32 · 2018: 31 · 2017: 42 · 2016: 36 · 2015: 47 · 2014: 44 · 2013: 28 · 2012: 56
FWCI: 18.04
Type: journal article
Language: en
Open access: closed
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Research Online (University of Wollongong) (submittedVersion)
Figshare (submittedVersion)
Funders: Diabetes Australia Research Trust
Diabetes Australia
Grains Research and Development Corporation
Juvenile Diabetes Research Foundation Australia
National Institutes of Health
Medical Research Council
National Health and Medical Research Council
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: insulin resistance, skeletal muscle insulin sensitivity, nonoxidative glucose disposal, lipid oxidation, glucose oxidation, obesity, adiposity, Pima Indians, vastus lateralis, euglycemic clamp
MeSH terms: Adult, Arizona, Biopsy, Body Composition, Body Constitution, Humans, Indians, North American, Insulin, Male, Obesity, Regression Analysis, Triglycerides, Glucose Clamp Technique, Muscle, Skeletal

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Skeletal Muscle Triglyceride Levels Are Inversely Related to Insulin Action

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