Insulin enhances transcription of the tyrosine aminotransferase gene in rat liver

Lee, Kai‐Lin; Isham, Kenneth R.; Johnson, Ann L.; Kenney, Francis T.

doi:10.1016/0003-9861(86)90513-8

Cited by 44 publications

(20 citation statements)

References 37 publications

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“…We also investigated the effects of vanadate on TAT, another enzyme related to gluconeogenesis and regulated at the level of gene expression in a similar manner as PEPCK (60-62). cAMP and glucocorticoids induce the expression of the gene whereas insulin inhibits TAT gene expression (63,64). In this study a similar pattern of modification (480±70% induction caused by diabetes and reduction to 180±38% after vanadate treatment) of the expression of the gene for TAT was detected (Fig.…”

Section: Resultssupporting

confidence: 80%

Vanadate treatment restores the expression of genes for key enzymes in the glucose and ketone bodies metabolism in the liver of diabetic rats.

Valera¹,

Rodríguez‐Gil²,

Bosch³

1993

J. Clin. Invest.

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Oral administration of vanadate to diabetic streptozotocintreated rats decreased the high blood glucose and D-3-hydroxybutyrate levels related to diabetes. The increase in the expression of the P-enolpyruvate carboxykinase (PEPCK) gene, the main regulatory enzyme of gluconeogenesis, was counteracted in the liver and the kidney after vanadate administration to diabetic rats. Vanadate also counteracted the induction in tyrosine aminotransferase gene expression due to diabetes and was able to increase the expression of the glucokinase gene to levels even higher than those found in healthy animals. Similarly, an induction in pyruvate kinase mRNA transcripts was observed in diabetic vanadate-treated rats. These effects were correlated with changes on glucokinase and pyruvate kinase activities. Vanadate treatment caused a decrease in the expression of the liver-specific glucose transporter, GLUT-2. Thus, vanadate was able to restore liver glucose utilization and block glucose production in diabetic rats. The increase in the expression of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCoAS) gene, the key regulatory enzyme in the ketone bodies production pathway, observed in diabetic rats was also blocked by vanadate. Furthermore, a similar pattern in the expression of PEPCK, GLUT-2, HMGCoAS, and the transcription factor CCAAT/ enhancer-binding protein a genes has been observed. All of these results suggest that the regulation of the expression of genes involved in the glucose and ketone bodies metabolism could be a key step in the normalization process induced by vanadate administration to diabetic rats. (J. Clin.

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Section: Resultssupporting

confidence: 80%

Vanadate treatment restores the expression of genes for key enzymes in the glucose and ketone bodies metabolism in the liver of diabetic rats.

Valera¹,

Rodríguez‐Gil²,

Bosch³

1993

J. Clin. Invest.

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“…An additional middle band (band C in Fig. 3c) CGCCTC present in various genes regulated by insulin, including c-myc and the genes encoding GH, ornithine decarboxylase, tyrosine aminotransferase, P33, and GAPDH (6,22,(24)(25)(26)(27). In the latter, two IREs appear to be present; in one of them, the minimal sequence contacted by an insulin-regulated DNA binding protein is CCCGCCTC, which has 6 of its 8 nucleotides homologous to the A domain of G3: CACGCCTG (6).…”

Section: +Insmentioning

confidence: 99%

Insulin regulation of the glucagon gene is mediated by an insulin-responsive DNA element.

Philippe¹

1991

Proc. Natl. Acad. Sci. U.S.A.

122

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Diabetes melfitus is characterized by insulin deficiency and high plasma glucagon levels, which can be normalized by insulin replacement. It has previously been reported that glucagon gene expression is negatively regulated by insulin at the transcriptional level. By transfection studies, I have now localized a DNA control element that mediates insulin effects on glucagon gene transcription. This element also confers insulin responsiveness to a heterologous promoter. DNA-binding proteins that specifically interact with this insulin-responsive element are found in both glucagon-and nonglucagon-producing cells; and the pattern of binding, as assessed by the gel retardation assay, is not modified by prior insulin treatment.Insulin regulates cell growth and promotes energy storage by interacting with its cell surface receptors (1). Some insulin effects occur through changes in gene expression; multiple examples of gene regulation by insulin at both transcriptional and posttranscriptional levels have been described in the last few years (2). However, the molecular mechanisms by which insulin mediates its cytoplasmic and nuclear effects are poorly understood. Characterization of cis-acting DNA sequences mediating insulin-induced modifications in gene transcription is a fundamental step leading to a better understanding of these mechanisms. Insulin-responsive elements (IREs) have recently been identified for the c-fos, phosphoenolpyruvate carboxykinase, amylase, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes (3-6). In contrast to most sequences that control common regulatory events, these IREs do not share any homology.Glucagon is a 29-amino acid peptide synthesized by the alpha cell of the pancreas and is involved in glucose homeostasis by directly activating gluconeogenesis and glycogenolysis. In diabetes mellitus, insulin deficiency is associated with high plasma glucagon levels, which rapidly return to normal with insulin treatment. In vitro, glucagon secretion and biosynthesis are inhibited by insulin (7-9). It has recently been shown that insulin effects on glucagon biosynthesis are mediated through a decrease in glucagon gene expression, which occurs at the transcriptional level (8, 9 GATCCTGAAGTAGYTrTCACGCCTGACTGAACGC-GAAGGGTGTAGC G3 mutant (G3M6) GATCCTGAAGTAGT1TT-lCAATTATGACTGAGATT-GAAGGGTGTAGCCell Culture and Transfection Studies. In-R1-G9, HeLa, and JEG-3 (a choriocarcinoma cell line) cells were cultured in RPMI 1640 containing 11 mM glucose, 5% fetal calf serum, and 5% newborn calf serum. In-R1-G9 cells were transfected in suspension by the DEAE-dextran method (10) with 3 ,ug of indicator plasmid and 1 j.g of each control plasmid, pxGH5 and pSV2Apap, to monitor transfection efficiency (12, 13). pSV2Apap is a plasmid containing the human placental alkaline phosphatase gene driven by the simian virus 40 long terminal repeat, and pxGH5 contains the human growth hormone (GH) sequence under the control of a metallothionein promoter. pRSVCAT and poCAT (11) were used as positive and negative ...

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“…Thus, the effect of insulin on the expression of the genes for tyrosine aminotransferase [22][23][24], glutamine synthetase [18,19], albumin [85,86], lipoprotein lipase [71][72][73] and the insulin receptor [48,49] varies with the cell line or primary cell culture studied, even though these cells originated from the same tissue. Moreover, in some cases such as adipsin [33,52] and growth hormone [66,68], the effect of insulin varies within clones of the same cell line.…”

Section: Miscellaneousmentioning

confidence: 99%

“…Gene 33* Thyroglobulin* T [13,14] T [15] 4 [16] T [17] T4 [18][19][20] T [21] T4 [22][23][24] 4 [25] [40], so it is difficult to sort out cause-effect relationships. This observation may explain the disparate results obtained with insulin between animals and tissue culture with regards expression of the c-fos [16,90], fatty acid synthetase [17,179], malic enzyme [43,44] and albumin [86,109] genes.…”

Section: Miscellaneousmentioning

confidence: 99%

Regulation of gene expression by insulin

O’Brien

Granner

1991

Biochemical Journal

271

106

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Insulin enhances transcription of the tyrosine aminotransferase gene in rat liver

Cited by 44 publications

References 37 publications

Vanadate treatment restores the expression of genes for key enzymes in the glucose and ketone bodies metabolism in the liver of diabetic rats.

Vanadate treatment restores the expression of genes for key enzymes in the glucose and ketone bodies metabolism in the liver of diabetic rats.

Insulin regulation of the glucagon gene is mediated by an insulin-responsive DNA element.

Regulation of gene expression by insulin

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