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

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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  • Muscle biopsy studies show increased triglyceride content in skeletal muscle of obese normal-glucose-tolerant subjects compared with lean individuals and an inverse relationship between muscle insulin sensitivity and intramuscular triglyceride content.

    “Muscle biopsy studies [53, 54] have demonstrated increased triglyceride content in skeletal muscle of obese NGT subjects compared to lean individuals and an inverse relationship between muscle insulin sensitivity and the intramuscular triglyceride content.”

    From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [53]

  • The mechanism by which obesity causes skeletal muscle insulin resistance is related to accumulation of fat within myocytes.

    “The mechanism via which obesity causes insulin resistance in skeletal muscle is related to the accumulation of fat in the myocytes.”

    From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [53]

  • Lipids interfere with insulin signaling and represent one of the key aspects that could contribute to insulin resistance in situations of high-fat feeding or lipid infusion.

    “These lipids interfere with insulin signaling and represent one of the key aspects that could contribute to insulin resistance in situations of high-fat feeding or lipid infusion (Pan et al, 1997; Krssak et al, 1999; Goodpaster et al, 2000).”

    From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Pan et al, 1997

  • Intramyocellular lipid levels were increased in first-level relatives of type 2 diabetes mellitus patients and were associated with impaired insulin-stimulated glucose uptake in muscle.

    “For instance, IMCL levels were increased in first-level relatives of T2DM patients and associated with impaired insulin-stimulated glucose uptake in muscle (Pan et al, 1997).”

    From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Pan et al, 1997

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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
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 › 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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