3,5,3′ Triiodo-L-thyronine Stimulates 2-Deoxy-D-Glucose Transport into L6 Muscle Cells Through the Phosphorylation of Insulin Receptor<i>β</i>and the Activation of PI-3k

Gordon, Amirav; Swartz, H. J.; Shwartz, Henia

doi:10.1089/thy.2006.16.521

Cited by 14 publications

(9 citation statements)

References 28 publications

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“…Although several studies have shown that triiodothyronine (T 3 ) may regulate glucose uptake and oxygen consumption (2, 3, 4, 5, 6, 7, 8), the effects of T 3 on glucose metabolism remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Thyroid states regulate subcellular glucose phosphorylation activity in male mice

Peçanha

Santos

da‐Silva

2017

Endocrine Connections

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The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are very important in organism metabolism and regulate glucose utilization. Hexokinase (HK) is responsible for the first step of glycolysis, catalyzing the conversion of glucose to glucose 6-phosphate. HK has been found in different cellular compartments, and new functions have been attributed to this enzyme. The effects of hyperthyroidism on subcellular glucose phosphorylation in mouse tissues were examined. Tissues were removed, subcellular fractions were isolated from eu- and hyperthyroid (T3, 0.25 µg/g, i.p. during 21 days) mice and HK activity was assayed. Glucose phosphorylation was increased in the particulate fraction in soleus (312.4% ± 67.1, n = 10), gastrocnemius (369.2% ± 112.4, n = 10) and heart (142.2% ± 13.6, n = 10) muscle in the hyperthyroid group compared to the control group. Hexokinase activity was not affected in brain or liver. No relevant changes were observed in HK activity in the soluble fraction for all tissues investigated. Acute T3 administration (single dose of T3, 1.25 µg/g, i.p.) did not modulate HK activity. Interestingly, HK mRNA levels remained unchanged and HK bound to mitochondria was increased by T3 treatment, suggesting a posttranscriptional mechanism. Analysis of the AKT pathway showed a 2.5-fold increase in AKT and GSK3B phosphorylation in the gastrocnemius muscle in the hyperthyroid group compared to the euthyroid group. Taken together, we show for the first time that THs modulate HK activity specifically in particulate fractions and that this action seems to be under the control of the AKT and GSK3B pathways.

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Section: Introductionmentioning

confidence: 99%

Thyroid states regulate subcellular glucose phosphorylation activity in male mice

Peçanha

Santos

da‐Silva

2017

Endocrine Connections

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“…In the studies of Segal (11,12), evidence was provided that these effects were mediated by a nongenomic pathway, as not only the onset of action was rapid, but also that the effects occurred in the presence of the protein synthesis inhibitor cycloheximide. More recently, Gordon et al obtained evidence that T 3 stimulated the uptake of 2-deoxy-D-glucose into L6 cells by a nongenomic pathway (13).…”

Section: Introductionmentioning

confidence: 99%

T₃Rapidly IncreasesSLC2A4Gene Expression and GLUT4 Trafficking to the Plasma Membrane in Skeletal Muscle of Rat and Improves Glucose Homeostasis

Brunetto

Teixeira

Giannocco

et al. 2012

Thyroid

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The results presented here show for the first time that, in parallel to its transcriptional action on the SLC2A4 gene, T(3) exerts a rapid post-transcriptional effect on GLUT4 mRNA polyadenylation, which might increase transcript stability and translation efficiency, leading to the increased GLUT4 content and availability to skeletal muscle, as well as on GLUT4 translocation to the PM, improving the insulin sensitivity, as shown by the kITT.

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“…Furuya et al (14) have also pointed out that the TR␤ mutant TR␤PV, via activation of the PI3-kinase-regulatory subunit p85␣, may affect PI3-kinase downstream signaling in both nuclear and extranuclear compartments, thus contributing to thyroid carcinogenesis. PI3-kinase appears to play a role in rapid nongenomic (15) and genomic actions of thyroid hormone (32), even though the significance and molecular mechanisms of many of these nongenomic actions are incompletely understood. Src kinase, another integrin ␣ v ␤ 3 -regulated kinase, has also been reported to be involved in T 3 -induced Na-K-ATPase activation and expression in alveolar epithelial cells (22).…”

mentioning

confidence: 99%

l-Thyroxine vs. 3,5,3′-triiodo-l-thyronine and cell proliferation: activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase

Lin¹,

Sun²,

Tang³

et al. 2009

American Journal of Physiology-Cell Physiology

234

236

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,5,3Ј-Triiodo-L-thyronine (T3), but not L-thyroxine (T4), activated Src kinase and, downstream, phosphatidylinositol 3-kinase (PI3-kinase) by means of an ␣ v␤3 integrin receptor on human glioblastoma U-87 MG cells. Although both T 3 and T4 stimulated extracellular signal-regulated kinase (ERK) 1/2, activated ERK1/2 did not contribute to T 3-induced Src kinase or PI3-kinase activation, and an inhibitor of PI3-kinase, LY-294002, did not block activation of ERK1/2 by physiological concentrations of T 3 and T4. Thus the PI3-kinase, Src kinase, and ERK1/2 signaling cascades are parallel pathways in T 3-treated U-87 MG cells. T3 and T4 both caused proliferation of U-87 MG cells; these effects were blocked by the ERK1/2 inhibitor PD-98059 but not by LY-294002. Smallinterfering RNA knockdown of PI3-kinase confirmed that PI3-kinase was not involved in the proliferative action of T 3 on U-87 MG cells. PI3-kinase-dependent actions of T 3 in these cells included shuttling of nuclear thyroid hormone receptor-␣ (TR␣) from cytoplasm to nucleus and accumulation of hypoxia-inducible factor (HIF)-1␣ mRNA; LY-294002 inhibited these actions. Results of studies involving ␣v␤3 receptor antagonists tetraiodothyroacetic acid (tetrac) and Arg-Gly-Asp (RGD) peptide, together with mathematical modeling of the kinetics of displacement of radiolabeled T3 from the integrin by unlabeled T3 and by unlabeled T4, are consistent with the presence of two iodothyronine receptor domains on the integrin. A model proposes that one site binds T3 exclusively, activates PI3-kinase via Src kinase, and stimulates TR␣ trafficking and HIF-1␣ gene expression. Tetrac and RGD peptide both inhibit T3 action at this site. The second site binds T4 and T3, and, via this receptor, the iodothyronines stimulate ERK1/2-dependent tumor cell proliferation. T3 action here is inhibited by tetrac alone, but the effect of T4 is blocked by both tetrac and the RGD peptide. thyroid hormone; phosphatidylinositol 3-kinase; extracellular signal-regulated kinase 1/2; integrin ␣v␤3; glioblastoma cells; Src kinase; mitogenactivated protein kinase; intracellular hormone receptor trafficking ACTIONS OF THYROID HORMONE [L-thyroxine (T 4 ); 3,5,3Ј-triiodo-L-thyronine (T 3 )] that are independent of ligand binding to nuclear thyroid hormone receptors are called nongenomic actions. Nongenomic effects of thyroid hormone are initiated outside the cell nucleus but may culminate in complex cellular events that are nucleus mediated (7, 8, 26 -29). Initiation of nongenomic actions includes a plasma membrane receptor for T 4 and T 3 on integrin ␣ v ␤ 3 that is linked to mitogen-activated protein kinase [extracellular signal-regulated kinase (ERK) 1/2] for transduction of the hormone signal (3) and nuclear receptors residing in the cytosol of unstimulated cells, such as thyroid hormone receptor (TR) ␤1 (28).The phosphatidylinositol 3-kinase (PI3-kinase)/protein kinase B (Akt) pathway is an important regulator of cellular growth, metabolism, and survival (13, 19). Studies of Storey et al. (38) indi...

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3,5,3′ Triiodo-L-thyronine Stimulates 2-Deoxy-D-Glucose Transport into L6 Muscle Cells Through the Phosphorylation of Insulin Receptorβand the Activation of PI-3k

Cited by 14 publications

References 28 publications

Thyroid states regulate subcellular glucose phosphorylation activity in male mice

Thyroid states regulate subcellular glucose phosphorylation activity in male mice

T₃Rapidly IncreasesSLC2A4Gene Expression and GLUT4 Trafficking to the Plasma Membrane in Skeletal Muscle of Rat and Improves Glucose Homeostasis

l-Thyroxine vs. 3,5,3′-triiodo-l-thyronine and cell proliferation: activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase

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3,5,3′ Triiodo-L-thyronine Stimulates 2-Deoxy-D-Glucose Transport into L6 Muscle Cells Through the Phosphorylation of Insulin Receptorβand the Activation of PI-3k

Cited by 14 publications

References 28 publications

Thyroid states regulate subcellular glucose phosphorylation activity in male mice

Thyroid states regulate subcellular glucose phosphorylation activity in male mice

T3Rapidly IncreasesSLC2A4Gene Expression and GLUT4 Trafficking to the Plasma Membrane in Skeletal Muscle of Rat and Improves Glucose Homeostasis

l-Thyroxine vs. 3,5,3′-triiodo-l-thyronine and cell proliferation: activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase

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Product

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T₃Rapidly IncreasesSLC2A4Gene Expression and GLUT4 Trafficking to the Plasma Membrane in Skeletal Muscle of Rat and Improves Glucose Homeostasis