Howard C. Towle

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In mammals, glucose-regulated gene expression has been best characterized in the liver, where increased glucose metabolism induces transcription of genes encoding enzymes involved in de novo lipogenesis. ChREBP and Mlx dimerize and function together as a glucose-responsive transcription factor to regulate target genes, such as liver-type pyruvate kinase,(More)
Thyroid hormone exerts profound effects on the developing mammalian brain, and its deficiency can lead to severe mental retardation and motor abnormalities. To identify specific anatomic targets of thyroid hormone action in the developing mammalian nervous system, we examined thyroid hormone receptor gene expression by hybridization histochemistry on serial(More)
Diets high in simple carbohydrates and low in fats lead in the mammalian liver to induction of a set of enzymes involved in lipogenesis. This induction occurs, in part, through transcriptional mechanisms that lead to elevated levels of the mRNA for these enzymes. For most of the lipogenic enzymes, an increase in glucose metabolism is required to trigger the(More)
The expression of genes encoding enzymes involved in de novo triglyceride synthesis (lipogenesis) is transcriptionally induced in the liver in response to increased glucose metabolism. The carbohydrate response element-binding protein (ChREBP) is a newly identified basic helix-loop-helix/leucine zipper transcription factor proposed to regulate the(More)
Adipocyte determination- and differentiation-dependent factor 1 (ADD1), a member of the basic helix-loop-helix (bHLH) family of transcription factors, has been associated with both adipocyte differentiation and cholesterol homeostasis (in which case it has been termed SREBP1). Using PCR-amplified binding analysis, we demonstrate that ADD1/SREBP1 has dual(More)
Carbohydrate response element-binding protein (ChREBP) is a glucose-responsive transcription factor that activates genes involved in de novo lipogenesis in mammals. The current model for glucose activation of ChREBP proposes that increased glucose metabolism triggers a cytoplasmic to nuclear translocation of ChREBP that is critical for activation. However,(More)
Chronically culturing HIT-T15 cells in media containing high glucose concentrations leads to decreased insulin mRNA levels, insulin content, and insulin secretion. These changes can be prevented by culturing the cells in media containing lower glucose levels (Robertson, R. P., H.-J. Zhang, K. L. Pyzdrowski, and T. F. Walseth. 1992. J. Clin. Invest.(More)
A growth hormone-inducible nuclear factor complex (GHINF), affinity-purified using the growth hormone response element (GHRE) from the promoter of rat serine protease inhibitor 2.1, was found to contain Stat5a and -5b, as well as additional components. The ubiquitous transcription factor yin-yang 1 (YY1) is present in GHINF. An antibody to YY1 inhibited the(More)
In the liver, a high glucose concentration activates transcription of genes encoding glucose 6-phosphatase and enzymes for glycolysis and lipogenesis by elevation in phosphorylated intermediates and recruitment of the transcription factor ChREBP (carbohydrate response element binding protein) and its partner, Mlx, to gene promoters. A proposed function for(More)
Glucose metabolism in the liver activates the transcription of various genes encoding enzymes of glycolysis and lipogenesis and also G6pc (glucose-6-phosphatase). Allosteric mechanisms involving glucose 6-phosphate or xylulose 5-phosphate and covalent modification of ChREBP (carbohydrate-response element-binding protein) have been implicated in this(More)