Effects of Thyroid Hormone on GLUT4 Glucose Transporter Gene Expression and NIDDM in Rats

Torrance, C; DeVente, James; Jones, J. P.; Dohm, G. Lynis

doi:10.1210/endo.138.3.4981

Cited by 84 publications

(37 citation statements)

References 41 publications

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“…The animals were randomly divided into two groups: control (n=8) and treated with triiodothyronine (T 3 ) (n=8). Triiodothyronine (Sigma Aldrich, St. Louis, MO) was injected subcutaneously at a dose of 50µg/100g of body weight, daily for 10 days, as reported elsewhere [25]. This dose is commonly used to mimic hyperthyroidism in humans [26].…”

Section: Methodsmentioning

confidence: 99%

Hyperthyroidism Evokes Myocardial Ceramide Accumulation

Mikłosz

Łukaszuk

Chabowski

et al. 2015

Cell Physiol Biochem

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Background: Thyroid hormones (THs) are key regulators of cardiac physiology as well as modulators of different cellular signals including the sphingomyelin/ceramide pathway. The objective of this study was to examine the effect of hyperthyroidism on the metabolism of sphingolipids in the muscle heart. Methods: Male Wistar rats were treated for 10 days with triiodothyronine (T₃) at a dose of 50µg/100g of body weight. Animals were then anaesthetized and samples of the left ventricle were excised. Results: We have demonstrated that prolonged, in vivo, T₃ treatment increased the content of sphinganine (SFA), sphingosine (SFO), ceramide (CER) and sphingomyelin (SM), but decreased the level of sphingosine-1-phosphate (S1P) in cardiac muscle. Accordingly, the changes in sphingolipids content were accompanied by a lesser activity of neutral sphingomyelinase and without significant changes in ceramidases activity. Hyperthyroidism also induced activation of AMP-activated protein kinase (AMPK) with subsequently increased expression of mitochondrial proteins: cytochrome c oxidase IV (COX IV), β-hydroxyacyl-CoA dehydrogenase (β-HAD), carnityne palmitoyltransferase I (CPT I) and nuclear peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α). Conclusions: We conclude that prolonged T₃ treatment increases sphingolipids metabolism which is reflected by higher concentration of SFA and CER in heart muscle. Furthermore, hyperthyroidism-induced increase in heart sphingomyelin (SM) concentration might be one of the mechanisms underlying maintenance of CER at relatively low level by its conversion to SM together with decreased S1P content.

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Section: Methodsmentioning

confidence: 99%

Hyperthyroidism Evokes Myocardial Ceramide Accumulation

Mikłosz

Łukaszuk

Chabowski

et al. 2015

Cell Physiol Biochem

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“…It is thus assumed that in the insulin deficient goats glucose is utilized in the hormones interactions. Thyroid hormones support the potential of hormonally inducing glucose transporter expression in insulin-resistant muscle as observed in NIDDM in rats [26]. It seems very likely with glucose lowering in hypoinsulinemic goats of the study as Weinstein et al reported that thyroid hormone increases even basal glucose transport in skeletal muscle with GLUT4 glucose transporter expression [27].…”

Section: Discussionmentioning

confidence: 82%

Effect of TRH and TSH on Circulatory Glucose and Fatty Acids Responses in Hypoinsulenemic Male Dwarf Goats

Mushtaq¹,

Mushtaq²,

Cheema³

et al. 2014

ABB

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Diabetes mellitus or hypoinsulinemia was induced successfully in the male dwarf goats aged between 2 -3 years with 2 consecutive administrations of streptozotocin. A comparable group of intact control goats was also maintained. In ruminants including goats unlike non-ruminants, insulin generally displays ineffectiveness or resistance in their biochemical setup to facilitate gluconeogenesis, the only source of glucose in these animals. In present study almost in the absence of insulin through induced hypoinsulinemia the effects of thyrotropin releasing hormone (TRH) (30 µg/kg body weight) and thyroid stimulating hormone (TSH) (2.5 µg/kg body weight) on circulatory glucose and different fatty acid fractions were studied in insulin resistant ruminant model. Fatty acid fractions were estimated by gas chromatography. Both TRH and TSH administration lowered glycemia in insulin deficient goats compared to the controls but significantly with TSH dose only. In intact goats the detectable circulating long chain fatty acids (LCFAs) fractions of lauric, myristic, palmitic, stearic, oleic and linoleic acid were undetected except linoleic acid in the hypoinsulinemic state, however were found restored following TRH and TSH administrations and some of LCFAs; stearic (6417%), oleic (1676%) and linoleic acid (1225%) increased exceptionally with TSH dose. In Intact goats however the hormones variedly increased the fractions. The volatile fatty acid fractions (VFAs) of formic, acetic, propionic, iso-butyric, n-butyric, iso-valeric, n-valeric, iso-caproic, n-caproic and heptanoic acid were detected in the goats. The most VFAs fractions markedly increased in hypoinsulinemic goats compared to the control goats following TRH and TSH infusion. These results have indicated that endogenously stimulated thyroid hormones with TRH and TSH in insulin deficient state inhibit the mechanisms of utilizing the fatty acids in glucose production. Therefore the study reveals thyroid hormones inhibitory effects on gluconeogenesis in insulin resistance and hyperglycemia.

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“…The relevance of the MEF2-binding site was also reported in a study using transgenic mice, in which a marked repression of the transcriptional activity driven by 895 bp of DNA encompassing the 5Ј-flanking region of GLUT4 gene was detected in adipose tissues or in muscles after mutation of the MEF2-binding site (18). It is surprising to find that the TRE inhibits the activity of the enhancer under normal conditions in adult muscle because: on the one hand, the administration of T 3 to rats is known to cause the induction of GLUT4 gene expression in certain muscle types (5,6); in addition, the concentration of T 3 in rat skeletal muscle lies within the nanomolar range (35), i.e. high enough to activate to some degree thyroid hormone receptors.…”

Section: Discussionmentioning

confidence: 99%

Differential Regulation of the Muscle-specific GLUT4 Enhancer in Regenerating and Adult Skeletal Muscle

Moreno

Serrano

Santalucı́a

et al. 2003

Journal of Biological Chemistry

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We have reported a novel functional co-operation among MyoD, myocyte enhancer factor-2 (MEF2), and the thyroid hormone receptor in a muscle-specific enhancer of the rat GLUT4 gene in muscle cells. Here, we demonstrate that the muscle-specific enhancer of the GLUT4 gene operates in skeletal muscle and is muscle fiber-dependent and innervation-independent. Under normal conditions, both in soleus and in extensor digitorum longus muscles, the activity of the enhancer required the integrity of the MEF2-binding site. Cancellation of the binding site of thyroid hormone receptor enhanced its activity, suggesting an inhibitory role. Muscle regeneration of the soleus and extensor digitorum longus muscles caused a marked induction of GLUT4 and stimulation of the enhancer activity, which was independent of innervation. During muscle regeneration, the enhancer activity was markedly inhibited by cancellation of the binding sites of MEF2, MyoD, or thyroid hormone receptors. Different MEF2 isoforms expressed in skeletal muscle (MEF2A, MEF2C, and MEF2D) and all members of the MyoD family had the capacity to participate in the activity of the GLUT4 enhancer as assessed by transient transfection in cultured cells. Our data indicate that the GLUT4 enhancer operates in muscle fibers and its activity contributes to the differences in GLUT4 gene expression between oxidative and glycolytic muscle fibers and to the GLUT4 up-regulation that occurs during muscle regeneration. The activity of the enhancer is maintained in adult muscle by MEF2, whereas during regeneration the operation of the enhancer depends on MEF2, myogenic transcription factors of the MyoD family, and thyroid hormone receptors.

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Effects of Thyroid Hormone on GLUT4 Glucose Transporter Gene Expression and NIDDM in Rats

Cited by 84 publications

References 41 publications

Hyperthyroidism Evokes Myocardial Ceramide Accumulation

Hyperthyroidism Evokes Myocardial Ceramide Accumulation

Effect of TRH and TSH on Circulatory Glucose and Fatty Acids Responses in Hypoinsulenemic Male Dwarf Goats

Differential Regulation of the Muscle-specific GLUT4 Enhancer in Regenerating and Adult Skeletal Muscle

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