Expression and function of the insulin receptor in normal and osteoarthritic human chondrocytes: modulation of anabolic gene expression, glucose transport and GLUT-1 content by insulin

We tested the hypothesis that an increase in cytosolic calcium concentration stimulates glucose transporter isoform (GLUT-1) gene expression. Exposure of a rat liver cell line (Clone 9) to 3 microM A-23187 for 12 h resulted in 3-, 5-, and 10-fold increases in cytochalasin B-inhibitable 3-O-methyl-D-glucose transport, GLUT-1 protein, and GLUT-1 mRNA content, respectively. The induction of GLUT-1 mRNA in response to A-23187 is not preceded by a significant decrease in cell ATP content. This induction is prevented by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid in conjunction with ethylene glycol-bis(beta-aminoethyl ether)-N,N, N',N'-tetraacetic acid. To investigate the mechanism of GLUT-1 mRNA induction, we found that exposure to A-23187 stabilized GLUT-1 mRNA: with the employment of actinomycin D, GLUT-1 mRNA had a half-life of 1.5 and 5.5 h in control and A-23187-treated cells, respectively. In nuclear run-on assays, the rate of GLUT-1 gene transcription was stimulated 1.5- to 1.7-fold in nuclei isolated from cells exposed to A-23187 for either 30 min or 2 h. These results demonstrate that exposure to A-23187 stimulates GLUT-1 gene expression and that the increase in GLUT-1 mRNA content is mediated in part by enhanced GLUT-1 gene transcription as well as decreased GLUT-1 mRNA degradation. The increase in GLUT-1 mRNA content, in turn, is associated with increased cell GLUT-1 content and enhanced glucose transport.

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Dexamethasone modulates insulin receptor expression and subcellular distribution of the glucose transporter GLUT 1 in UMR 106-01, a clonal osteogenic sarcoma cell line

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0170007 ◽

1996 ◽

Vol 17 (1) ◽

pp. 7-17 ◽

Cited By ~ 10

Author(s):

D M Thomas ◽

S D Rogers ◽

K W Ng ◽

J D Best

Keyword(s):

Plasma Membrane ◽

Insulin Receptor ◽

Glucose Transport ◽

Glucose Transporter ◽

Insulin Binding ◽

Receptor Expression ◽

Glut 1 ◽

Receptor Mrna ◽

Insulin Receptor Expression ◽

Umr 106

ABSTRACT Corticosteroids have profound effects on bone metabolism, though the underlying mechanisms remain unclear. They are also known to alter glucose metabolism, in part by induction of insulin resistance. To determine whether corticosteroids impair glucose metabolism in bone cells, we have examined the actions of dexamethasone (DEX) on glucose transport and insulin receptor expression using osteoblast-like UMR 106-01 cells. DEX was shown to inhibit basal 2-deoxyglucose uptake by up to 30% in a time- and dose-dependent manner. It inhibited insulin-stimulated glucose transport by 13%. By Northern and Western blot analysis, DEX was shown to stimulate insulin receptor mRNA and protein by up to 5·6-fold, but it had no effect on expression of the glucose transporter GLUT 1 mRNA or protein under basal conditions. However, DEX augmented insulin-stimulated GLUT 1 mRNA and protein levels. By Scatchard analysis of labelled insulin binding, DEX increased insulin receptor number per cell by 54%. Subcellular fractionation and Western blot analysis demonstrated that DEX caused a redistribution of immunoreactive GLUT 1 from plasma membrane to intracellular microsomes, resulting in a 21% decrease in GLUT 1 at the plasma membrane. These data suggest that (i) DEX impairs basal glucose transport by post-translational mechanisms in UMR 106-01 cells, (ii) DEX increases insulin receptor mRNA, protein and insulin binding and (iii) the inhibition of glucose transport by DEX dominates its effects on the insulin receptor. It is possible that DEX inhibition of glucose transport in osteoblasts may contribute to steroid-induced osteoporosis.

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Thyroid hormone increases the partitioning of glucose transporters to the plasma membrane in ARL 15 cells

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.269.3.e605 ◽

1995 ◽

Vol 269 (3) ◽

pp. E605-E610

Author(s):

R. S. Haber ◽

C. M. Wilson ◽

S. P. Weinstein ◽

A. Pritsker ◽

S. W. Cushman

Keyword(s):

Gene Expression ◽

Plasma Membrane ◽

Cell Surface ◽

Glucose Transport ◽

Glucose Transporter ◽

Transporter Gene ◽

Glut 1 ◽

Surface Partitioning ◽

Enhanced Surface ◽

Stimulation Of

The stimulation of glucose transport by 3,5,3'-triiodo-L-thyronine (T3) in the liver-derived ARL 15 cell line is only partly attributable to increased GLUT-1 glucose transporter gene expression. To test the hypothesis that T3 increases the partitioning of GLUT-1 to the cell surface, we quantitated surface GLUT-1 using the photolabel ATB-[3H]BMPA. In control cells only approximately 20% of total cellular GLUT-1 was present at the cell surface. T3 treatment (100 nM) for 6 h increased the rate of 2-deoxy-[3H]glucose (2-DG) uptake by 30, 92, and 95% in three experiments and increased surface GLUT-1 photolabeling by 17, 81, and 72%, respectively, with no increase in total cellular GLUT-1. T3 treatment for 48 h increased 2-DG uptake by 143, 172, and 216% in three experiments and increased cell surface GLUT-1 photolabeling by 88, 161, and 184%, respectively, with smaller increases in total cellular GLUT-1. T3 treatment for 48 h thus increased the fraction of cellular GLUT-1 at the plasma membrane from 21 +/- 2 to 35 +/- 3% (SE). We conclude that most of the early (6-h) stimulation of glucose transport by T3 in ARL 15 cells is mediated by an increase in the partitioning of GLUT-1 to the plasma membrane. With more chronic T3 treatment (48 h), the enhanced surface partitioning of GLUT-1 is persistent and is superimposed on an increase in total cellular GLUT-1, accounting for a further increase in glucose transport.

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Growth restriction in the rat alters expression of metabolic genes during postnatal cardiac development in a sex-specific manner

Physiological Genomics ◽

10.1152/physiolgenomics.00095.2012 ◽

2013 ◽

Vol 45 (3) ◽

pp. 99-105 ◽

Cited By ~ 16

Author(s):

Glenn D. Wadley ◽

Glenn K. McConell ◽

Craig A. Goodman ◽

Andrew L. Siebel ◽

Kerryn T. Westcott ◽

...

Keyword(s):

Gene Expression ◽

Glucose Transport ◽

Mitochondrial Biogenesis ◽

Cardiac Development ◽

Growth Restriction ◽

Antioxidant Defenses ◽

Postnatal Life ◽

Male And Female ◽

Glut 1 ◽

The Impact

This study investigated the impact of uteroplacental insufficiency and growth restriction on the expression of genes related to mitochondrial biogenesis, glucose transport, and antioxidant defenses in cardiac tissue at embryonic day 20 (E20) and postnatal days 1, 7, and 35 in male and female Wistar rats (8–10 per group). Bilateral uterine vessel ligation to induce growth restriction (Restricted) or sham surgery was performed at pregnancy day 18. In male and female Controls, expression of most cardiac genes decreased during postnatal life, including genes involved in mitochondrial biogenesis regulation such as PGC-1α, NRF-2, and mtTFA and the glucose transporter GLUT-1 ( P < 0.05). However, the pattern of gene expression during cardiac development differed in male and female Restricted rats compared with their respective Controls. These effects of restriction were observed at postnatal day 1, with female Restricted rats having delayed reductions in PGC-1α and GLUT-1, whereas males had exacerbated reductions in PGC-1α and mtTFA ( P < 0.05). By day 35, cardiac gene expression in Restricted hearts was similar to Controls, except for expression of the antioxidant enzyme MnSOD, which was significantly lower in both sexes. In summary, during postnatal life male and female Control rats have similar patterns of expression for genes involved in mitochondrial biogenesis and glucose transport. However, following uteroplacental insufficiency these gene expression patterns diverge in males and females during early postnatal life, with MnSOD gene expression reduced in later postnatal life.

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Faculty Opinions recommendation of Altered gene expression and function of peripheral blood natural killer cells in children with autism.

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

10.3410/f.1120723.576960 ◽

2008 ◽

Author(s):

Isaac Kohane

Keyword(s):

Gene Expression ◽

Natural Killer Cells ◽

Natural Killer ◽

Peripheral Blood ◽

Children With Autism ◽

Killer Cells ◽

Altered Gene Expression ◽

Altered Gene ◽

And Function

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Faculty Opinions recommendation of LEF1-mediated MMP13 gene expression is repressed by SIRT1 in human chondrocytes.

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

10.3410/f.727488527.793556145 ◽

2019 ◽

Author(s):

David Young

Keyword(s):

Gene Expression ◽

Human Chondrocytes

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Roles of HIF and 2-Oxoglutarate-Dependent Dioxygenases in Controlling Gene Expression in Hypoxia

Cancers ◽

10.3390/cancers13020350 ◽

2021 ◽

Vol 13 (2) ◽

pp. 350

Author(s):

Julianty Frost ◽

Mark Frost ◽

Michael Batie ◽

Hao Jiang ◽

Sonia Rocha

Keyword(s):

Gene Expression ◽

Hypoxia Inducible Factor ◽

Transcriptional Regulator ◽

Hydroxylase Activity ◽

Control Of Gene Expression ◽

Prolyl Hydroxylases ◽

Chromatin Organisation ◽

Sense And Respond ◽

Almost All ◽

And Function

Hypoxia—reduction in oxygen availability—plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OGDs in the control of gene expression in response to hypoxia and their relevance to human biology and health.

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Testicular Melatonin and Its Pathway in Roe Deer Bucks (Capreolus capreolus) during Pre- and Post-Rut Periods: Correlation with Testicular Involution

Animals ◽

10.3390/ani11071874 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1874

Author(s):

Alberto Elmi ◽

Nadia Govoni ◽

Augusta Zannoni ◽

Martina Bertocchi ◽

Chiara Bernardini ◽

...

Keyword(s):

Gene Expression ◽

Correlation Analysis ◽

Roe Deer ◽

Capreolus Capreolus ◽

Reproductive Activity ◽

Melatonin Receptors ◽

Local Synthesis ◽

Testicular Weight ◽

And Function ◽

Gene Expression Levels

Roe deer are seasonal breeders with a complete yearly testicular cycle. The peak in reproductive activity is recorded during summer, the rutting period, with the highest levels of androgens and testicular weight. Melatonin plays a pivotal role in seasonal breeders by stimulating the hypothalamus–pituitary–gonads axis and acting locally; in different species, its synthesis within testes has been reported. The aim of this study was to evaluate the physiological melatonin pattern within roe deer testes by comparing data obtained from animals sampled during pre- and post-rut periods. Melatonin was quantified in testicular parenchyma, along with the genetic expression of enzymes involved in its local synthesis (AANAT and ASMT) and function (UCP1). Melatonin receptors, MT1-2, were quantified both at protein and gene expression levels. Finally, to assess changes in reproductive hormonal profiles, testicular dehydroepiandrosterone (DHEA) was quantified and used for a correlation analysis. Melatonin and AANAT were detected in all samples, without significant differences between pre- and post-rut periods. Despite DHEA levels confirming testicular involution during the post-rut period, no correlations appeared between such involution and melatonin pathways. This study represents the first report regarding melatonin synthesis in roe deer testes, opening the way for future prospective studies in the physiology of this species.

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