Intramuscular triglyceride and muscle insulin sensitivity: Evidence for a relationship in nondiabetic subjects
Abstract
Intracellular triglyceride (TG) is an important energy source for skeletal muscle. However, recent evidence suggests that if muscle contains abnormally high TG stores its sensitivity to insulin may be reduced, and this could predispose to type II diabetes. To test this hypothesis, we measured muscle lipid content in 27 women aged 47 to 55 years (mean, 52) and related it to their glucose tolerance, insulin resistance, and muscle insulin sensitivity as measured by insulin activation of glycogen synthase, an insulin-regulated enzyme that is rate-limiting for insulin action in muscle. Both muscle TG content and intracellular lipid determined by Oil red O staining of muscle fibers were negatively associated with glycogen synthase activation (r = .43, P = .03 and r = -.47, P = .02, respectively). In addition, intracellular lipid correlated with features of the insulin resistance syndrome, including an increased waist to hip ratio (r = .47, P = .01) and fasting nonesterified fatty acids ([NEFA] r = .44, P = .04). These data demonstrate that increased muscle TG stores are associated with decreased insulin-stimulated glycogen synthase activity. Intracellular fat may underlie a major part of the insulin resistance in normal subjects, as well as type II diabetics.
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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 [54]
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 [54]
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- Authors
- Phillips, D. I. W., Caddy, S., Ilic, V., Fielding, B. A., Frayn, K. N., Borthwick, A. C., & Taylor, R.
- Affiliations
- Southampton General Hospital (GB)
- Corresponding author
- Phillips, D.I.W.
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 1996-08
- Volume
- 45
- Issue
- 8
- Pages
- 947-950
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W2075703747
- Cited by
- 390
- References
- 24
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 5 · 2022: 7 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 11 · 2016: 11 · 2015: 8 · 2014: 9 · 2013: 9 · 2012: 13
- FWCI
- 6.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Open Research (University of Surrey) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- intramuscular triglycerides, skeletal muscle insulin sensitivity, insulin resistance, glycogen synthase activation, intracellular lipids, type 2 diabetes, free fatty acids, waist-to-hip ratio, glucose tolerance
- MeSH terms
- Body Constitution, Female, Humans, Insulin Resistance, Middle Aged, Muscles, Reference Values, Triglycerides, Lipid Metabolism
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