Glucose Regulation of Gene Transcription

Vaulont, Sophie; Vasseur-Cognet, Mireille; Kahn, Axel

doi:10.1074/jbc.r000016200

Cited by 256 publications

(177 citation statements)

References 83 publications

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“…However, the specific glucose-sensing mechanism and pathways in the BMEC are yet to be elucidated in detail. It is reported that eukaryotic cells take signals from the glycolytic and the pentose phosphate pathway metabolites to sense glucose availability through the action of protein kinase and transcription factors, such as stimulatory protein-1 (Vaulont et al, 2000;Towle, 2005).…”

Section: Discussionmentioning

confidence: 99%

Effect of glucose availability on glucose transport in bovine mammary epithelial cells

Zhao

Liu

Wang

et al. 2012

Animal

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Primary bovine mammary epithelial cells (BMEC) were cultured in media containing varying concentrations of glucose, to determine the effects of glucose availability on glucose transport and its mechanism in bovine mammary gland. The BMEC incubated with 10 and 20 mM glucose had twofold greater glucose uptake than that with 2.5 mM glucose (P , 0.05). Increased glucose availability enhanced the cell proliferation (P , 0.05). As the glucose uptake is mediated by facilitative glucose transporters (GLUTs), the expression of GLUT mRNA was investigated. Compared with the control (2.5 mM), 5 and 10 mM glucose did not influence the abundance of GLUT1 mRNA (P , 0.05), whereas 20 mM glucose decreased the GLUT1 mRNA expression in the BMEC (P , 0.05). The expression of GLUT8 mRNA was not affected by any concentration of glucose (P . 0.05). As GLUTs are coupled with hexokinases (HKs) in regulating glucose uptake, the expression of HKs and their activities were also studied. The HK activity was greater in 5, 10 and 20 mM glucose than that in 2.5 mM glucose (P , 0.05). The expression of HK2 mRNA rather than HK1 mRNA was detected in the BMEC; however, the abundance of HK2 mRNA was not elevated by any concentrations of glucose compared with control (P . 0.05). Furthermore, addition of 3-bromopyruvate (30, 50 or 70 mM), an inhibitor of HK2, resulted in the decrease of glucose uptake and cell proliferation at both 2.5 and 10 mM glucose (P , 0.05). Therefore, the glucose concentrations may affect glucose uptake partly by altering the activity of HKs, and HK2 may play an important role in the regulation of glucose uptake in the BMEC.

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Section: Discussionmentioning

confidence: 99%

Effect of glucose availability on glucose transport in bovine mammary epithelial cells

Zhao

Liu

Wang

et al. 2012

Animal

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“…During glycolysis, the cell undergoes various forms of stresses, when subjected to high-glucose ambience with inductive transcription of a wide variety of genes (38). In addition to glycative and osmotic stress, the oxidative stress related to reactive oxygen species has been well described in the literature (2,9).…”

Section: Discussionmentioning

confidence: 99%

Modulation of renal-specific oxidoreductase/ myo -inositol oxygenase by high-glucose ambience

Nayak¹,

Xie²,

Akagi³

et al. 2005

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

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Biological properties of renal-specific oxidoreductase (RSOR), characteristics of its promoter, and underlying mechanisms regulating its expression in diabetes were analyzed. RSOR expression, normally confined to the renal cortex, was markedly increased and extended into the outer medullary tubules in db͞db mice, a model of type 2 diabetes. Exposure of LLCPK cells to D-glucose resulted in a dose-dependent increase in RSOR expression and its enzymatic activity. The latter was related to one of the glycolytic enzymes, myo-inositol oxygenase. The increase in activity was in proportion to serum glucose concentration. The RSOR expression also increased in cells treated with various organic osmolytes, e.g., sorbitol, myoinositol, and glycerolphosphoryl-choline and H 2O2. Basal promoter activity was confined to ؊1,252 bp upstream of ATG, and it increased with the treatment of high glucose and osmolytes. EMSAs indicated an increased binding activity with osmotic-, carbohydrate-, and oxidant-response elements in cells treated with high glucose and was abolished by competitors. Supershifts, detected by anti-nuclear factor of activated T cells, and carbohydrate-response-element-binding protein established the binding specificity. Nuclear factor of activated T cells tonicityenhancer-binding protein and carbohydrate-response-elementbinding protein had increased nuclear expression in cells treated with high glucose. The activity of osmotic-response element exhibited a unique alternate binding pattern, as yet unreported in osmoregulatory genes. Data indicate that RSOR activity is modulated by diverse mechanisms, and it is endowed with dual properties to channel glucose intermediaries, characteristic of hepatic aldehyde reductases, and to maintain osmoregulation, a function of renal medullary genes, e.g., aldose reductase, in diabetes. diabetic nephropathy ͉ hyperglycemia ͉ osmoregulation D iabetic nephropathy is characterized by hyperplasia͞ hypertrophy of intrinsic renal cells and increased extracellular matrices (1). These changes are related to the increased cellular flux of glucose intermediaries (2), de novo synthesis of intra-and extracellular advanced glycation end products (3, 4), activation of protein kinase C (5, 6), increased expression of transforming growth factor-␤ (7), increased activity of GTP-binding and cell-cycle proteins (6,8), and generation of reactive oxygen species (9, 10), with consequential compromise in renal functions (11,12). Such complex interrelated cellular signaling events, also involving various forms of MAP͞ERK kinases and Smad proteins, have been defined mainly in glomerular cells (13,14); information relevant to the tubulointerstitial cells, although notably affected, is limited (15, 16). Conceivably, cellular changes in the tubulointerstitium parallel those in the glomerulus, with scarring and thickening of the basement membranes, and they correlate relatively better with the derangements in renal functional parameters (17, 18). Thus, much attention is warranted to the understanding of the...

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“…The expression of the genes for several other proteins is regulated by glucose; these include genes for L-type pyruvate kinase (13,14), fatty-acid synthase (15,16), PEPCK (17,18), and the type 2 glucose transporter (GLUT-2) (19,20). The mechanism by which glucose regulates the expression of these genes remains largely unknown.…”

Section: From the Department Of Nutrition Case Western Reserve Univementioning

confidence: 99%

Regulation of the Glucose-6-phosphatase Gene by Glucose Occurs by Transcriptional and Post-transcriptional Mechanisms

Massillon¹

2001

Journal of Biological Chemistry

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To understand how glucose regulates the expression of the glucose-6-phosphatase gene, the effect of glucose was studied in primary cultures of rat hepatocytes. Glucose-6-phosphatase mRNA levels increased about 10-fold when hepatocytes were incubated with 20 mM glucose. The rate of transcription of the glucose-6-phosphatase gene increased about 3-fold in hepatocytes incubated with glucose. The half-life of glucose-6-phosphatase mRNA was estimated to be 90 min in the absence of glucose and 3 h in its presence. Inhibition of the oxidative and the nonoxidative branches of the pentose phosphate pathway blocked the stimulation of glucose-6-phosphatase expression by glucose but not by xylitol or carbohydrates that enter the glycolytic/gluconeogenic pathways at the level of the triose phosphates. These results indicate that (i) the glucose induction of the mRNA for the catalytic unit of glucose-6-phosphatase occurs by transcriptional and post-transcriptional mechanisms and that (ii) xylitol and glucose increase the expression of this gene through different signaling pathways.Glc-6-Pase 1 (EC 3.1.3.9) is a multicomponent protein complex comprising catalytic and transporting entities (1-5). The complex is tightly associated with the endoplasmic reticulum, and the enzymatic component catalyzes the hydrolysis of glucose 6-phosphate to glucose, a final common step to both the pathways of glycogenolysis and gluconeogenesis. Hepatic Glc-6-Pase activity is effectively regulated by hormonal and nutritional status. For example, fasting and hormones that increase cAMP concentration stimulate its gene expression while refeeding and insulin decrease it (1, 2, 6 -12).The expression of the genes for several other proteins is regulated by glucose; these include genes for L-type pyruvate kinase (13, 14), fatty-acid synthase (15, 16), PEPCK (17, 18), and the type 2 glucose transporter (GLUT-2) (19,20). The mechanism by which glucose regulates the expression of these genes remains largely unknown. Recently, Kahn and colleagues (21, 22) have proposed a signaling pathway model to explain the molecular mechanism by which glucose regulates the expression of the L-type pyruvate kinase. This model consists of the following details: (i) the presence of glucose is sensed in the cell; (ii) this information is transduced by intracellular messengers; (iii) a second messenger, presumably xylulose 5-phosphate, rises and then modulates the activity of protein kinase and protein phosphatase involved in a cascade of phosphorylation/dephosphorylation. This cascade then leads to a modification of the phosphorylation state of the glucoseresponsive complex, followed by an increase in the transcriptional rate of the target gene. In this model, the presence of an active glucokinase that phosphorylates glucose to glucose 6-phosphate (Glc-6-P) is paramount.The molecular mechanism by which glucose regulates the expression of the Glc-6-Pase gene is currently unknown. Here we show that glucose regulation of the expression of this gene involves metabolism of glucose...

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Glucose Regulation of Gene Transcription

Cited by 256 publications

References 83 publications

Effect of glucose availability on glucose transport in bovine mammary epithelial cells

Effect of glucose availability on glucose transport in bovine mammary epithelial cells

Modulation of renal-specific oxidoreductase/ myo -inositol oxygenase by high-glucose ambience

Regulation of the Glucose-6-phosphatase Gene by Glucose Occurs by Transcriptional and Post-transcriptional Mechanisms

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