Abstract
Purpose
Diabetes mellitus (DM) has a multifactorial etiology that imparts a particular challenge to effective pharmacotherapy. Thyroid hormone actions have demonstrated beneficial effects in diabetic as well as obese rats. In both conditions, inflammation status plays a crucial role in the development of insulin resistance. Taking this into consideration, the present study aimed to demonstrate another possible pathway of thyroid hormone action on insulin sensitivity in a spontaneous type 2 diabetic rat model: the Goto–Kakizaki (GK) rats. GK animals present all typical hallmarks of type 2 DM (T2DM), except the usual peripheric inflammatory condition, observed in the other T2DM animal models.
Methods
GK rats were treated or not with 3,5,3′triiodothyronine (T3). Insulin sensitivity, glucose tolerance, and proteins related to glucose uptake and utilization were evaluated in the skeletal muscle, white adipose tissue, and liver.
Results
GK rats T3-treated presented enhanced insulin sensitivity, increased GLUT-4 content in the white adipose tissue and skeletal muscle, and increased hexokinase and citrate synthase content in skeletal muscle. Both non-treated and T3-treated GK rats did not present alterations in cytokine content in white adipose tissue, skeletal muscle, liver, and serum.
Conclusions
These results indicate that T3 improves insulin sensitivity in diabetic rats by a novel inflammatory-independent mechanism.
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Abbreviations
- CCL-2:
-
C–C motif chemokine ligand 2
- DM:
-
diabetes mellitus
- GK:
-
Goto–Kakizaki
- GTT:
-
glucose tolerance test
- GLUT-4:
-
glucose transporter type 4
- IL-1α:
-
interleukin 1 alpha
- IL-1β:
-
interleukin 1 beta
- IL-6:
-
interleukin 6
- IL-10:
-
interleukin 10
- ITT:
-
insulin tolerance test
- PCK:
-
phosphoenolpyruvate carboxykinase 1
- PYGM:
-
glycogen phosphorylase
- T3:
-
3,5,3′triiodothyronine
- TNF-α:
-
tumor necrosis factor alpha
- TSH:
-
thyroid-stimulating hormone
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Acknowledgements
We are grateful to Dr Tatiane Alba Loureiro for all scientific support during this study.
Funding
This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (Grant nos. 2013/05629-4 and 2017/21875-6); Conselho Nacional de Pesquisa e Desenvolvimento (Grant nos. 309437/2017-2 and 402332/2014-8).
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The Animal Ethical Committee of the Institute of Biomedical Sciences of the University of São Paulo (number 109/2013) approved all experimental procedures of this study.
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Panveloski-Costa, A.C., Kuwabara, W.M.T., Munhoz, A.C. et al. The insulin resistance is reversed by exogenous 3,5,3′triiodothyronine in type 2 diabetic Goto–Kakizaki rats by an inflammatory-independent pathway. Endocrine 68, 287–295 (2020). https://doi.org/10.1007/s12020-020-02208-5
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DOI: https://doi.org/10.1007/s12020-020-02208-5