Effects of thyroid hormone on UTP content and uridine kinase activity of rat heart and skeletal muscle

In rats made hyperthyroid by daily intramuscular injections of 250 microgram thyroxine (T4)/100 g body wt for 5 days, uridine kinase activity of extracts of psoas and cardiac muscle was markedly increased Vmax of the enzyme was elevated with no change in the apparent Km for uridine. In animals treated as above, significant increases in UTP and total uracil nucleotide contents were observed in heart and skeletal muscle. Twelve hours after a single intraperitoneal injection of 30 microgram/100 g body wt of 3,5,3'-triiodothyronine (T3), cardiac uridine kinase was significantly increased. Brain uridine kinase was unaffected by thyroid hormone treatment. In thyroidectomized rats, uridine kinase activity was lower than normal. The effect of thyroidectomy on uridine kinase activity was overcome by daily subcutaneous injections of 3 microgram T4/100 g body wt for 7 days. The rise in cardiac uridine kinase activity produced by T3 could be prevented by prior administration of actinomycin D.

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Differential modulation of expression of the two acylphosphatase isoenzymes by thyroid hormone

Biochemical Journal ◽

10.1042/bj3110567 ◽

1995 ◽

Vol 311 (2) ◽

pp. 567-573 ◽

Cited By ~ 6

Author(s):

P Chiarugi ◽

G Raugei ◽

R Marzocchini ◽

T Fiaschi ◽

C Ciccarelli ◽

...

Keyword(s):

Skeletal Muscle ◽

Thyroid Hormone ◽

State Level ◽

K562 Cells ◽

Hormone Treatment ◽

Differential Regulation ◽

Rapid Decrease ◽

Differential Modulation ◽

Hormone Administration ◽

Specific Mrna

The modulation of expression of the skeletal muscle and erythrocyte acylphosphatase isoenzymes by thyroid hormone has been investigated. Our results indicate a differential regulation of the two enzymic isoforms by tri-iodothyronine (T3) in K562 cells in culture: an increase in the specific mRNA during T3-stimulation is shown only for the skeletal muscle isoenzyme. A fast and transient T3 induction of the accumulation of the specific mRNA can be observed, reaching a maximum 8 h after hormone treatment and then rapidly decreasing almost to the steady-state level after 24 h. A nuclear run-on assay was performed to explore the mechanisms of this regulation. These studies indicate that T3 induction of skeletal muscle acylphosphatase mRNA is due, at least in part, to a fast and transient increase in the rate of gene transcription, within 4 h after hormone administration. A very rapid decrease is then observed within a further 2 h. T3-dependent accumulation of the mRNA for the skeletal muscle acylphosphatase requires ongoing protein synthesis, as confirmed by inhibition with cycloheximide or puromycin. These findings indicate that the transcriptional regulation of the gene may be indirect.

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Effect of diabetes and fasting on the uridine triphosphate content and uridine kinase activity of rat cardiac and skeletal muscle

Metabolism ◽

10.1016/0026-0495(79)90107-0 ◽

1979 ◽

Vol 28 (4) ◽

pp. 358-362 ◽

Cited By ~ 9

Author(s):

Barry J. Gertz ◽

Ella S. Haugaard

Keyword(s):

Skeletal Muscle ◽

Kinase Activity ◽

Uridine Triphosphate ◽

Uridine Kinase

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Na+,K+-ATPase enzyme units in lean and obese (ob/ob) thyroxine-injected mice.

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1979.237.3.e265 ◽

1979 ◽

Vol 237 (3) ◽

pp. E265

Author(s):

M H Lin ◽

J G Vander Tuig ◽

D R Romsos ◽

T Akera ◽

G A Leveille

Keyword(s):

Skeletal Muscle ◽

Thyroid Hormone ◽

Large Dose ◽

Binding Sites ◽

Hormone Treatment ◽

Obese Mice ◽

Ouabain Binding ◽

Hindlimb Muscles

The possible involvement of Na+,K+-ATPase in the etiology of obesity in the obese (ob/ob) mouse was explored. The number of Na+,K+-ATPase enzyme units in skeletal muscle, liver, and kidneys from 4- and 8-wk-old obese and lean mice was estimated from saturable [3H]ouabain binding to particulate fractions. Neither phenotype nor age altered the Kd value for ouabain binding in these three tissue preparations. The total number of [3H]ouabain binding sites in hindlimb muscles was 35--55% lower in 4- and 8-wk-old obese mice than in their lean counterparts. However, the total number of [3H]ouabain binding sites in liver and kidneys of obese mice was similar to values observed in their lean counterparts. Because it has been suggested that ob/ob mice are hypothyroid, we investigated the response of Na+,K+-ATPase in these mice to thyroid hormone treatment (approximately 5 microgram thyroxine/day for 2 wk). The number of [3H]ouabain binding sites in the three tissues increased in both obese and lean mice injected with this relatively large dose of thyroxine, but the obese mice were 2--3 times more responsive than lean mice.

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Thyroid hormone effects on LKB1, MO25, phospho-AMPK, phospho-CREB, and PGC-1α in rat muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.00997.2007 ◽

2008 ◽

Vol 105 (4) ◽

pp. 1218-1227 ◽

Cited By ~ 30

Author(s):

D. J. Branvold ◽

D. R. Allred ◽

D. J. Beckstead ◽

H. J. Kim ◽

N. Fillmore ◽

...

Keyword(s):

Skeletal Muscle ◽

Thyroid Hormone ◽

Thyroid Hormones ◽

Uncoupling Protein ◽

Mitochondrial Protein ◽

Hormone Treatment ◽

Peroxisome Proliferator ◽

Hexokinase Ii ◽

Hormone Synthesis ◽

Ampk Activity

Expression of all of the isoforms of the subunits of AMP-activated protein kinase (AMPK) and AMPK activity is increased in skeletal muscle of hyperthyroid rats. Activity of AMPK in skeletal muscle is regulated principally by the upstream kinase, LKB1. This experiment was designed to determine whether the increase in AMPK activity is accompanied by increased expression of the LKB1, along with binding partner proteins. LKB1, MO25, and downstream targets were determined in muscle extracts in control rats, in rats given 3 mg of thyroxine and 1 mg of triiodothyronine per kilogram chow for 4 wk, and in rats given 0.01% propylthiouracil (PTU; an inhibitor of thyroid hormone synthesis) in drinking water for 4 wk (hypothyroid group). LKB1 and MO25 increased in the soleus of thyroid hormone-treated rats vs. the controls. In other muscle types, LKB1 responses were variable, but MO25 increased in all. In soleus, MO25 mRNA increased with thyroid hormone treatment, and STRAD mRNA increased with PTU treatment. Phospho-AMPK and phospho-ACC were elevated in soleus and gastrocnemius of hyperthyroid rats. Thyroid hormone treatment also increased the amount of phospho-cAMP response element binding protein (CREB) in the soleus, heart, and red quadriceps. Four proteins having CREB response elements (CRE) in promoter regions of their genes (peroxisome proliferator-activated receptor-γ coactivator-1α, uncoupling protein 3, cytochrome c, and hexokinase II) were all increased in soleus in response to thyroid hormones. These data provide evidence that thyroid hormones increase soleus muscle LKB1 and MO25 content with subsequent activation of AMPK, phosphorylation of CREB, and expression of mitochondrial protein genes having CRE in their promoters.

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Faculty Opinions recommendation of Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: US national assessment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727247808.793529058 ◽

2017 ◽

Author(s):

John Walsh

Keyword(s):

Thyroid Hormone ◽

Pregnant Women ◽

Subclinical Hypothyroidism ◽

Hormone Treatment ◽

National Assessment

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Linear modulation of serum thyrotrophin by thyroid hormone treatment in hypothyroidism

Acta Endocrinologica ◽

10.1530/acta.0.0950472 ◽

1980 ◽

Vol 95 (4) ◽

pp. 472-478 ◽

Cited By ~ 6

Author(s):

A. Eugene Pekary ◽

Jerome M. Hershman ◽

Clark T. Sawin

Keyword(s):

Thyroid Hormone ◽

Hormone Replacement ◽

Hormone Treatment ◽

Significant Negative Correlation ◽

Thyroid Hormone Replacement ◽

Basal Serum ◽

Thyroid Hormone Levels ◽

Peak Versus ◽

Hypothyroid Patients ◽

Serum Tsh

Abstract. Basal serum TSH and the peak TSH response to a 500 μg TRH bolus were measured in 57 euthyroid and in 29 hypothyroid subjects either receiving graded thyroid hormone replacement or acutely removed from full replacement therapy. Serum TSH, total T4 and T3 were determined by sensitive radioimmunoassay methods. The peak versus basal TSH data for hypothyroid patients were linear within individuals. The regression slope of the peak versus basal TSH data for all hypothyroid subjects did not differ significantly from the corresponding slope for all euthyroid subjects. Basal and peak TSH versus T3 and T4 data for hypothyroid patients were also linear within each individual. Moreover, the regression of the basal TSH values averaged over the non-replacement to full replacement state against the TSH versus T3 slope had a significant negative correlation. This trend leads to an array of regression lines which average to the familiar hyperbolic relationship between thyrotrophin and thyroid hormone levels in man.

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ATP x Mg-dependent protein phosphatase from rabbit skeletal muscle. II. Purification of the activating factor and its characterization as a bifunctional protein also displaying synthase kinase activity.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)70200-2 ◽

1980 ◽

Vol 255 (24) ◽

pp. 11768-11774 ◽

Cited By ~ 5

Author(s):

J.R. Vandenheede ◽

S.D. Yang ◽

J. Goris ◽

W. Merlevede

Keyword(s):

Skeletal Muscle ◽

Protein Phosphatase ◽

Kinase Activity ◽

Rabbit Skeletal Muscle ◽

Bifunctional Protein ◽

Dependent Protein

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Creatine kinase activity of urinary bladder and skeletal muscle from control and streptozotocin-diabetic rats

Molecular and Cellular Biochemistry ◽

10.1007/bf00221057 ◽

1990 ◽

Vol 97 (2) ◽

Cited By ~ 4

Author(s):

RobertM. Levin ◽

PenelopeA. Longhurst ◽

SheilaS. Levin ◽

Niels Haugaard ◽

AlanJ. Wein

Keyword(s):

Skeletal Muscle ◽

Creatine Kinase ◽

Urinary Bladder ◽

Kinase Activity ◽

Diabetic Rats ◽

Creatine Kinase Activity ◽

Streptozotocin Diabetic Rats

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NF-κB-Inducing Kinase (NIK) Mediates Skeletal Muscle Insulin Resistance: Blockade by Adiponectin

Endocrinology ◽

10.1210/en.2011-1343 ◽

2011 ◽

Vol 152 (10) ◽

pp. 3622-3627 ◽

Cited By ~ 26

Author(s):

Sanjeev Choudhary ◽

Sandeep Sinha ◽

Yanhua Zhao ◽

Srijita Banerjee ◽

Padma Sathyanarayana ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Glucose Uptake ◽

Kinase Activity ◽

Pi3 Kinase ◽

Dominant Negative ◽

Muscle Insulin Resistance ◽

Akt Phosphorylation ◽

Skeletal Muscle Insulin Resistance ◽

Obese Subjects

Enhanced levels of nuclear factor (NF)-κB-inducing kinase (NIK), an upstream kinase in the NF-κB pathway, have been implicated in the pathogenesis of chronic inflammation in diabetes. We investigated whether increased levels of NIK could induce skeletal muscle insulin resistance. Six obese subjects with metabolic syndrome underwent skeletal muscle biopsies before and six months after gastric bypass surgery to quantitate NIK protein levels. L6 skeletal myotubes, transfected with NIK wild-type or NIK kinase-dead dominant negative plasmids, were treated with insulin alone or with adiponectin and insulin. Effects of NIK overexpression on insulin-stimulated glucose uptake were estimated using tritiated 2-deoxyglucose uptake. NF-κB activation (EMSA), phosphatidylinositol 3 (PI3) kinase activity, and phosphorylation of inhibitor κB kinase β and serine-threonine kinase (Akt) were measured. After weight loss, skeletal muscle NIK protein was significantly reduced in association with increased plasma adiponectin and enhanced AMP kinase phosphorylation and insulin sensitivity in obese subjects. Enhanced NIK expression in cultured L6 myotubes induced a dose-dependent decrease in insulin-stimulated glucose uptake. The decrease in insulin-stimulated glucose uptake was associated with a significant decrease in PI3 kinase activity and protein kinase B/Akt phosphorylation. Overexpression of NIK kinase-dead dominant negative did not affect insulin-stimulated glucose uptake. Adiponectin treatment inhibited NIK-induced NF-κB activation and restored insulin sensitivity by restoring PI3 kinase activation and subsequent Akt phosphorylation. These results indicate that NIK induces insulin resistance and further indicate that adiponectin exerts its insulin-sensitizing effect by suppressing NIK-induced skeletal muscle inflammation. These observations suggest that NIK could be an important therapeutic target for the treatment of insulin resistance associated with inflammation in obesity and type 2 diabetes.

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