Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults

Fleischman, Amy; Johnsen, Stine; Systrom, David M.; Hrovat, Mirko; Farrar, Christian T.; Frontera, Walter; Fitch, Kathleen; Thomas, Bijoy J.; Torriani, Martin; Côté, Hélène C. F.; Grinspoon, Steven K.

doi:10.1152/ajpendo.00550.2006

Cited by 160HIV-related health complications and treatmentsMetabolism, Diabetes, and CancerMitochondrial Function and Pathology

Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults

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Fleischman, Amy, Johnsen, Stine, Systrom, David M., Hrovat, Mirko, Farrar, Christian T., Frontera, Walter, Fitch, Kathleen, Thomas, Bijoy J. +3 more·2007·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.00550.2006PMC PMC3206591

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Abstract

Mitochondrial dysfunction may contribute to the development of insulin resistance and type 2 diabetes. Nucleoside reverse transcriptase inhibitors (NRTIs), specifically stavudine, are known to alter mitochondrial function in human immunodeficiency virus (HIV)-infected individuals, but the effects of stavudine on glucose disposal and mitochondrial function in muscle have not been prospectively evaluated. In this study, we investigated short-term stavudine administration among healthy control subjects to determine effects on insulin sensitivity. A secondary aim was to determine the effects of stavudine on mitochondrial DNA (mtDNA) and function. Sixteen participants without personal or family history of diabetes were enrolled. Subjects were randomized to receive stavudine, 30–40 mg, twice a day, or placebo for 1 mo. Insulin sensitivity determined by glucose infusion rate during the hyperinsulinemic euglycemic clamp was significantly reduced after 1-mo exposure in the stavudine-treated subjects compared with placebo (−0.8 ± 0.5 vs. +0.7 ± 0.3 mg·kg−1·min−1, P = 0.04, stavudine vs. placebo). In addition, muscle biopsy specimens in the stavudine-treated group showed significant reduction in mtDNA/nuclear DNA (−52%, P = 0.005), with no change in placebo-treated subjects (+8%, P = 0.9).31 P magnetic resonance spectroscopy (MRS) studies of mitochondrial function correlated with insulin sensitivity measures ( r 2= 0.5, P = 0.008). These findings demonstrate that stavudine administration has potent effects on insulin sensitivity among healthy subjects. Further studies are necessary to determine whether changes in mtDNA resulting from stavudine contribute to effects on insulin sensitivity.

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Insulin sensitivity is decreased in healthy individuals treated with NRTI stavudine.
“Insulin sensitivity was also decreased in healthy individuals treated with the NRTI stavudine (Fleischman et al, 2007).”
From The struggle of a good friend getting old: cellular senescence in viral responses and therapy (2021) · cites this paper as Fleischman et al, 2007

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Authors: Fleischman, A., Johnsen, S., Systrom, D. M., Hrovat, M., Farrar, C. T., Frontera, W., Fitch, K., Thomas, B. J., Torriani, M., Côté, H. C. F., & Grinspoon, S. K.
Affiliations: Massachusetts General Hospital (US)
ORCID: Fleischman, Amy
Johnsen, Stine
Systrom, David M.
Hrovat, Mirko
Farrar, Christian T.
Frontera, Walter
Fitch, Kathleen
Torriani, Martin
Côté, Hélène C. F.
Grinspoon, Steven K.
Venue: American Journal of Physiology-Endocrinology and Metabolism
Publisher: American Physiological Society
Published: 2007-06
Volume: 292
Issue: 6
Pages: E1666-E1673
ISSN: 0193-1849 (ISSN-L)
1522-1555
DOI: 10.1152/ajpendo.00550.2006
PMC: PMC3206591
OpenAlex: W2091454493
Cited by: 160
References: 21
Citations by year: 2025: 1 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 7 · 2018: 10 · 2017: 6 · 2016: 6 · 2015: 7 · 2014: 12 · 2013: 10 · 2012: 9
FWCI: 21.57
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Massachusetts General Hospital
Deutsches Krebsforschungszentrum
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK059535, R01 DK 59535, P30DK040561)
National Center for Research Resources (M01RR001066, M01-RR01066)
Topics: Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords: stavudine, nucleoside reverse transcriptase inhibitors, insulin sensitivity, insulin resistance, glucose disposal, skeletal muscle, mitochondrial DNA, mitochondrial dysfunction, type 2 diabetes, hyperinsulinemic-euglycemic clamp, 31P NMR
MeSH terms: Adult, Body Composition, DNA, Mitochondrial, Female, Glucose, Humans, Insulin Resistance, Male, Middle Aged, Mitochondria, Muscle, Magnetic Resonance Spectroscopy, Phosphocreatine, Phosphorus, Protons, Glucose Clamp Technique, Stavudine, Muscle, Skeletal, Reverse Transcriptase Inhibitors

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Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults

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