Tissue-Specific Changes in Insulin Receptor mRNA Concentrations in Dexamethasone-Treated and Adrenalectomized Rats.

Leal, M. A.; Aller, Patricio; Más, Antonio; Carranza, Carmen; Calle, C.

doi:10.1507/endocrj.41.737

Cited by 9 publications

(3 citation statements)

References 28 publications

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“…While dexamethasone has similar effects in these cell lines, not all tissues responded identically in an intact animal. Dexamethasone treatment of rats induced three-fold INSR expression in the liver, but no change was observed in adipocytes, indicating tissue specificity [84].…”

Section: Evidence For Specific Regulation Of Insr Transcription By Endogenous and Exogenous Stimulimentioning

confidence: 91%

Transcriptional Regulation of INSR, the Insulin Receptor Gene

Payankaulam

Raicu

Arnosti

2019

Genes

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The insulin receptor gene encodes an evolutionarily conserved signaling protein with a wide spectrum of functions in metazoan development. The insulin signaling pathway plays key roles in processes such as metabolic regulation, growth control, and neuronal function. Misregulation of the pathway features in diabetes, cancer, and neurodegenerative diseases, making it an important target for clinical interventions. While much attention has been focused on differential pathway activation through ligand availability, sensitization of overall signaling may also be mediated by differential expression of the insulin receptor itself. Although first characterized as a “housekeeping” gene with stable expression, comparative studies have shown that expression levels of the human INSR mRNA differ by tissue and in response to environmental signals. Our recent analysis of the transcriptional controls affecting expression of the Drosophila insulin receptor gene indicates that a remarkable amount of DNA is dedicated to encoding sophisticated feedback and feed forward signals. The human INSR gene is likely to contain a similar level of transcriptional complexity; here, we summarize over three decades of molecular biology and genetic research that points to a still incompletely understood regulatory control system. Further elucidation of transcriptional controls of INSR will provide the basis for understanding human genetic variation that underlies population-level physiological differences and disease.

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Section: Evidence For Specific Regulation Of Insr Transcription By Endogenous and Exogenous Stimulimentioning

confidence: 91%

Transcriptional Regulation of INSR, the Insulin Receptor Gene

Payankaulam

Raicu

Arnosti

2019

Genes

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“…A couple of papers have demonstrated that the addition of insulin to cultured hepatocytes or hepatomas decreases the half-life of CYP2E1 mRNA and that inhibition of the insulin signal pathway restores the insulin-mediated decrease in CYP2E1 mRNA levels (Woodcroft and Novak, 1997;Woodcroft et al, 2002). Since adipocytes are one of the main targets of insulin action, and the mRNA level of the insulin receptor in white adipose tissue was as high as in the liver (Leal et al, 1994;unpublished data), it is reasonable to assume that the mechanism reported in the liver or hepatocytes is also functional in adipose tissue. In addition to transcriptional and post-transcriptional regulation, CYP2E1 induction is also regulated at the post-translational level.…”

Section: Discussionmentioning

confidence: 99%

Expression and Induction of Cytochromes P450 in Rat White Adipose Tissue

Yoshinari¹,

Satô²,

Okino³

et al. 2004

J Pharmacol Exp Ther

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Lipophilic environmental pollutants are often stored in adipose tissues after exposure. These compounds have been well studied in terms of their cell toxicity in organs such as liver and kidney, and their xenoestrogenic action on reproductive tissues as endocrine disruptors. However, the effects of these chemicals on the depot, adipose tissue, have not been studied, although adipose tissue is an important endocrine tissue secreting obesity/diabetes-related hormones and cytokines. In this study, we identified the expression of cytochromes P450 in rat white adipose tissues and investigated the effects of typical lipophilic cytochrome P450 inducers, namely phenobarbital, dexamethasone, and ␤-naphthoflavone. The results showed that ␤-naphthoflavone was a strong CYP1A inducer in adipose tissue as well as in liver. It increased CYP1A1 mRNA, protein, and its related activity, ethoxyresorufin O-deethylase. Phenobarbital and dexamethasone also induced both the mRNA and protein of CYP2Bs and CYP3As, respectively, in adipose tissue, although significant interindividual differences were observed. Furthermore, we demonstrated that 48 h of fasting was as effective in adipose tissue as in the liver in the induction of CYP2E1 mRNA and protein. These results suggest that the mechanisms by which cytochrome P450 genes are regulated in the liver are also functional in rat adipose tissues. This has raised the possibility that lipophilic environmental contaminants accumulated in adipose tissue may dysregulate the gene expression profile.

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“…It is now well known that DEX augments the abundance of tissue-specific mRNA in several tissues, including liver. [15][16][17][18][19][20] Many effects of DEX on gene expression are mediated through the intracellular glucocorticoid receptor whereas others occur through nontranscriptional means via secondary messenger cascades. 21 DEX binds to the glucocorticoid receptor in the cytoplasm of target cells.…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone Effects on Rat Hepatocyte Spheroid Formation and Function

Abu-Absi

Hansen

2005

Tissue Engineering

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Hepatocytes cultured on moderately adhesive surfaces or in spinner flasks spontaneously self-assemble into spherical tissue-like aggregates (spheroids). These spheroids have smooth surfaces and tissue-like polarized cell morphology, including bile canalicular-like channels, and maintain high viability and liver-specific functions for extended culture periods. Dexamethasone (DEX), a synthetic glucocorticoid, is known to elicit various responses in gene expression, and is often added to hepatocyte culture medium. The morphology and liver-specific protein production of hepatocyte spheroids were assessed under DEX concentrations ranging from 50 nM to 10 microM. DEX altered the kinetics of spheroid formation in a concentration-dependent fashion, with increasing concentrations inhibiting aggregation and promoting aggregate disassembly on culture dishes. DEX addition to spinner cultures resulted in smaller, more irregularly shaped spheroids and a higher incidence of aggregate clumping. Albumin and urea production were also higher in DEX cultures, but this effect was not as sensitive to concentration and occurred irrespective of the state of aggregation. RTPCR was utilized to assess the mRNA levels of extracellular matrix proteins, E-cadherin, and cytochrome P-450 enzymes. Results indicated a slight increase in fibronectin and collagen III mRNA early in the cultures, possibly contributing to the changes in morphology observed.

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Tissue-Specific Changes in Insulin Receptor mRNA Concentrations in Dexamethasone-Treated and Adrenalectomized Rats.

Cited by 9 publications

References 28 publications

Transcriptional Regulation of INSR, the Insulin Receptor Gene

Transcriptional Regulation of INSR, the Insulin Receptor Gene

Expression and Induction of Cytochromes P450 in Rat White Adipose Tissue

Dexamethasone Effects on Rat Hepatocyte Spheroid Formation and Function

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