Cited by 48Thyroid Disorders and TreatmentsAdrenal Hormones and DisordersExercise and Physiological Responses

Skeletal muscle deiodinase type 2 regulation during illness in mice

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Kwakkel, J, van Beeren, H C, Ackermans, M T, Platvoet-ter Schiphorst, M C, Fliers, E, Wiersinga, W M, Boelen, A·2009·Journal of Endocrinology

Abstract

We have previously shown that skeletal muscle deiodinase type 2 ( D2 ) mRNA (listed as Dio2 in MGI Database) is upregulated in an animal model of acute illness. However, human studies on the expression of muscle D2 during illness report conflicting data. Therefore, we evaluated the expression of skeletal muscle D2 and D2-regulating factors in two mouse models of illness that differ in timing and severity of illness: 1) turpentine-induced inflammation, and 2) Streptococcus pneumoniae infection. During turpentine-induced inflammation, D2 mRNA and activity increased compared to pair-fed controls, most prominently at day 1 and 2, whereas after S. pneumoniae infection D2 mRNA decreased. We evaluated the association of D2 expression with serum thyroid hormones, (de-)ubiquitinating enzymes ubiquitin-specific peptidase 33 and WD repeat and SOCS box-containing 1 ( Wsb1 ), cytokine expression and activation of inflammatory pathways and cAMP pathway. During chronic inflammation the increased muscle D2 expression is associated with the activation of the cAMP pathway. The normalization of D2 5 days after turpentine injection coincides with increased Wsb1 and tumor necrosis factor α expression. Muscle interleukin-1β ( Il1b ) expression correlated with decreased D2 mRNA expression after S. pneumoniae infection. In conclusion, muscle D2 expression is differentially regulated during illness, probably related to differences in the inflammatory response and type of pathology. D2 mRNA and activity increases in skeletal muscle during the acute phase of chronic inflammation compared to pair-fed controls probably due to activation of the cAMP pathway. In contrast, muscle D2 mRNA decreases 48 h after a severe bacterial infection, which is associated with local Il1b mRNA expression and might also be due to diminished food-intake.

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  • Muscle DIO2 is differentially affected during illness: acute inflammation in mice increases muscle Dio2 mRNA expression, while bacterial sepsis decreases Dio2 mRNA expression both in mice and humans.

    “Muscle DIO2 is differentially affected during illness. Acute inflammation in mice increases muscle Dio2 mRNA expression, while bacterial sepsis decreases Dio2 mRNA expression both in mice [28] and humans [29].”

    From An update on non-thyroidal illness syndrome (2021) · cites this paper as [28]

  • Chronic inflammation in mice results in simultaneously increased DIO2 and DIO3 activity.

    “In contrast, chronic inflammation in mice results in simultaneously increased DIO2 and DIO3 activity [28].”

    From An update on non-thyroidal illness syndrome (2021) · cites this paper as [28]

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  1. Eds LE Braverman & RD Utiger. Philadelphia: Lippincott. Wiersinga WM & Chopra IJ 1982 Radioimmunoassay of thyroxine (T 4 ), 3,5,3 0 -triiodothyronine (T 3 ), 3,3 0 ,5 0 -triiodothyronine (reverse T 3 , rT 3 ), and 3,3 0 -diiodothyronine (T 2 ). Methods in Enzymology 84 272-303.

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Authors
Kwakkel, J., van Beeren, H. C., Ackermans, M. T., Platvoet-ter Schiphorst, M. C., Fliers, E., Wiersinga, W. M., & Boelen, A.
Affiliations
Amsterdam UMC Location University of Amsterdam (NL)
Venue
Journal of Endocrinology
Published
2009-08-05
Volume
203
Issue
2
Pages
263-270
ISSN
  • 0022-0795 (ISSN-L)
  • 1479-6805
OpenAlex
W2110009389
Cited by
48
References
42
Citations by year
2026: 1 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 1 · 2012: 5
FWCI
4.37
Type
journal article
Language
en
Open access
Locations
  • Journal of Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
Keywords
DIO2, acute illness, turpentine-induced inflammation, pneumococcal infection, cAMP pathway, WSB1, TNF-α, IL-1β, thyroid hormone regulation, chronic inflammation, bacterial infection, dietary intake
MeSH terms
Iodothyronine Deiodinase Type II, Animals, Female, Inflammation, Iodide Peroxidase, Mice, Inbred C57BL, Phosphorylation, Pneumococcal Infections, RNA, Messenger, Thyroid Hormones, Turpentine, Signal Transduction, Gene Expression Regulation, Enzymologic, Cyclic AMP Response Element-Binding Protein, Muscle, Skeletal, Ubiquitin-Protein Ligases, Intracellular Signaling Peptides and Proteins, Mice, Interleukin-1beta

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