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. 2017 Mar;232(3):501-511.
doi: 10.1530/JOE-16-0428. Epub 2016 Dec 15.

Exogenous thyroxine improves glucose intolerance in insulin-resistant rats

Guillermo Vazquez-Anaya  1 , Bridget Martinez  2 , José G Soñanez-Organis  3 , Daisuke Nakano  4 , Akira Nishiyama  4 , Rudy M Ortiz  2
Affiliations

Exogenous thyroxine improves glucose intolerance in insulin-resistant rats

Guillermo Vazquez-Anaya et al. J Endocrinol. 2017 Mar.

Abstract

Both hypothyroidism and hyperthyroidism are associated with glucose intolerance, calling into question the contribution of thyroid hormones (TH) on glucose regulation. TH analogues and derivatives may be effective treatment options for glucose intolerance and insulin resistance (IR), but their potential glucoregulatory effects during conditions of impaired metabolism are not well described. To assess the effects of thyroxine (T4) on glucose intolerance in a model of insulin resistance, an oral glucose tolerance test (oGTT) was performed on three groups of rats (n = 8): (1) lean, Long Evans Tokushima Otsuka (LETO), (2) obese, Otsuka Long Evans Tokushima Fatty (OLETF) and (3) OLETF + T4 (8.0 µg/100 g BM/day × 5 weeks). T4 attenuated glucose intolerance by 15% and decreased IR index (IRI) by 34% in T4-treated OLETF compared to untreated OLETF despite a 31% decrease in muscle Glut4 mRNA expression. T4 increased the mRNA expressions of muscle monocarboxylate transporter 10 (Mct10), deiodinase type 2 (Di2), sirtuin 1 (Sirt1) and uncoupling protein 2 (Ucp2) by 1.8-, 2.2-, 2.7- and 1.4-fold, respectively, compared to OLETF. Activation of AMP-activated protein kinase (AMPK) and insulin receptor were not significantly altered suggesting that the improvements in glucose intolerance and IR were independent of enhanced insulin-mediated signaling. The results suggest that T4 treatment increased the influx of T4 in skeletal muscle and, with an increase of DI2, increased the availability of the biologically active T3 to upregulate key factors such SIRT1 and UCP2 involved in cellular metabolism and glucose homeostasis.

Keywords: OLETF rat; glucose intolerance; insulin-resistant rat; thyroxine.

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Conflict of interest statement

Declaration of Interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Figures

Figure 1
Figure 1
Mean (±SE)(A) food consumption, (B) BM throughout the course of the study, and (C) cumulative change of BM of LETO, OLETF, and OLETF+T4. †, P<0.05 vs. LETO.
Figure 2
Figure 2
Mean (±SE) (A) blood glucose and (B) plasma insulin levels taken during an oral glucose tolerance test and corresponding area under the curve (AUC) and (C) insulin resistance index (IRI) of LETO, OLETF, and OLETF+T4. †, P<0.05 vs. LETO. #, P<0.05 vs. OLETF.
Figure 3
Figure 3
Mean (±SE) (A) TSH, (B) total T4, and (C) free T4 (fT4), and (D) total T3 measured in plasma of LETO, OLETF, and OLETF+T4. †, P<0.05 vs. LETO. #, P<0.05 vs. OLETF.
Figure 4
Figure 4
Mean (±SE) percent change from LETO for Na+/K+ ATPase in soleus muscle of LETO, OLETF, and OLETF+T4 after 5 wk treatment and representative Western blot bands. †, P<0.05 vs. LETO. #, P<0.05 vs. OLETF.
Figure 5
Figure 5
Mean (±SE) fold change of mRNA expression relative to LETO for (A) MCT10, (B) DI1, (C) DI2, (D) THRβ-1, (E) UCP2, and (F) SIRT 1 in soleus muscle of LETO, OELTF, and OLETF+T4 after 5 wk treatment. †, P<0.05 vs. LETO. #, P<0.05 vs. OLETF.
Figure 6
Figure 6
Mean (±SE) percent change from LETO for the ratios of (A) p-INS to INS (B) p-AMPK to AMPK including representative Western blot bands and (C) mean fold change of mRNA expression relative to LETO for GLUT 4 in soleus muscle of LETO, OLETF, and OLETF+T4 after 5 wk treatment. #, P<0.05 vs. OLETF.
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References

    1. Aguer C, Harper M-E. Skeletal muscle mitochondrial energetics in obesity and type 2 diabetes mellitus: endocrine aspects. Best Practice & Research. Clinical Endocrinology & Metabolism. 2012;26:805–819. doi: 10.1016/j.beem.2012.06.001. - DOI - PubMed
    1. Araujo RL, de Andrade BM, de Figueiredo ÁSP, da Silva ML, Marassi MP, dos Pereira VS, Bouskela E, Carvalho DP. Low replacement doses of thyroxine during food restriction restores type 1 deiodinase activity in rats and promotes body protein loss. Journal of Endocrinology. 2008;198:119–125. doi: 10.1677/JOE-08-0125. - DOI - PubMed
    1. Bernal J, Refetoff S. The action of thyroid hormone. Clinical Endocrinology. 1977;6:227–249. - PubMed
    1. Brandon AE, Tid-ang J, Wright LE, Stuart E, Suryana E, Bentley N, Turner N, Cooney GJ, Ruderman B, Kraegen EW. Overexpression of SIRT1 in Rat Skeletal Muscle Does Not Alter Glucose Induced Insulin Resistance. 2015:1–12. doi: 10.1371/journal.pone.0121959. - DOI - PMC - PubMed
    1. Brenta G. Diabetes and thyroid disorders. The British Journal of Diabetes & Vascular Disease. 2010;10(4):172–177.

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