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Growth hormone-induced insulin resistance is associated with increased intramyocellular triglyceride content but unaltered VLDL-triglyceride kinetics
Abstract
The ability of growth hormone (GH) to stimulate lipolysis and cause insulin resistance in skeletal muscle may be causally linked, but the mechanisms remain obscure. We investigated the impact of GH on the turnover of FFA and VLDL-TG, intramuscular triglyceride content (IMTG), and insulin sensitivity (euglycemic clamp) in nine healthy men in a randomized double-blind placebo-controlled crossover study after 8 days treatment with (A) Placebo+Placebo, (B) GH (2 mg daily)+Placebo, and (C) GH (2 mg daily)+Acipimox (250 mgx3 daily). In the basal state, GH (B) increased FFA levels (P<0.05), palmitate turnover (P<0.05), and lipid oxidation (P=0.05), but VLDL-TG kinetics were unaffected. Administration of acipimox (C) suppressed basal lipolysis but did not influence VLDL-TG kinetics. In the basal state, IMTG content increased after GH (B; P=0.03). Insulin resistance was induced by GH irrespective of concomitant acipimox (P<0.001). The turnover of FFA and VLDL-TG was suppressed by hyperinsulinemia during placebo and GH, whereas coadministration of acipimox induced a rebound increase FFA turnover and VLDL-TG clearance. We conclude that these results show that GH-induced insulin resistance is associated with increased IMTG and unaltered VLDL-TG kinetics; we hypothesize that fat oxidation in muscle tissue is an important primary effect of GH and that circulating FFA rather than VLDL-TG constitute the major source for this process; and the role of IMTG in the development of GH-induced insulin resistance merits future research.
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“Although growth hormone (GH) secretion occurs largely during the N3 sleep (23), GH is unlikely to be a factor in the associations, as GH increases insulin resistance (24) rather than insulin secretion.”
From Sleep architecture and glucose and insulin homeostasis in obese adolescents (2011) · cites this paper as [24]
Citations
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Yang, J., Zhao, Y., Pu, Y., Chen, Y., Chen, Y., Yi, L., Liu, P. Y., & Chen, C. (2026) · Journal of Endocrinology · doi:10.1530/joe-25-0416
Metadata
- Authors
- Krag, M. B., Gormsen, L. C., Guo, Z., Christiansen, J. S., Jensen, M. D., Nielsen, S., & Jørgensen, J. O. L.
- Affiliations
- Aarhus University Hospital (DK)
- Aarhus University (DK)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2007-03
- Volume
- 292
- Issue
- 3
- Pages
- E920-E927
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2135012391
- Cited by
- 101
- References
- 51
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 7 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 7 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 6 · 2014: 8 · 2013: 7 · 2012: 9
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- growth hormone, insulin resistance, intramyocellular triglyceride, free fatty acid turnover, acipimox, lipolysis, hyperinsulinemic-euglycemic clamp, fat oxidation
- MeSH terms
- Adult, Body Weight, Calorimetry, Indirect, Fatty Acids, Nonesterified, Glucose, Humans, Insulin Resistance, Insulin-Like Growth Factor I, Lipoproteins, VLDL, Male, Placebos, Growth Hormone, Triglycerides, Muscle Fibers, Skeletal
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