Glucose Regulation of Gene Transcription
Year: 2000
Type: review
Abstract: L-type pyruvate kinase acetyl-CoA carboxylase spot 14 AMP-activated protein kinase glucose response element carbohydrate response element chicken ovalbumin upstream promoter-transcription factor upstream stimulatory factor sterol response element-binding protein phosphatidylinositol 3-kinase pancreatic duodenum homeobox 1 Nutrient gene regulation is an important adaptation allowing survival on intermittent food supplies. This adaptative process exists in all species from yeast to mammals. Glucose, the most abundant monosaccharide in nature, provides a very good example of how organisms have developed regulatory mechanisms to cope with a fluctuating level of nutrient supply. In yeast, glucose facilitates its own use by inducing expression of genes involved in its metabolism while repressing that of those involved in the utilization of alternative carbon sources (for review, see Ref. 1Johnston M. Trends Genet. 1999; 15: 29-33Abstract Full Text Full Text PDF PubMed Scopus (318) Google Scholar). The mechanisms by which glucose affects gene expression in yeast are now relatively well understood. In mammals the response to dietary glucose is more complex because it combines effects related to glucose metabolism itself and effects secondary to glucose-dependent hormonal modifications, mainly pancreatic stimulation of insulin secretion and inhibition of glucagon secretion. In the pancreatic β cells, glucose is the primary physiological stimulus for the regulation of insulin synthesis and secretion. In the liver, glucose, in the presence of insulin, induces expression of genes encoding glucose transporters and glycolytic and lipogenic enzymes, e.g. L-type pyruvate kinase (L-PK),1 acetyl-CoA carboxylase (ACC), and fatty acid synthase, and represses genes of the gluconeogenic pathway, such as the phosphoenolpyruvate carboxykinase gene (for review, see Refs. 2Vaulont S. Kahn A. FASEB J. 1994; 8: 28-35Crossref PubMed Scopus (174) Google Scholar, 3Girard J. Ferre P. Foufelle F. Annu. Rev. Nutr. 1997; 17: 325-352Crossref PubMed Scopus (302) Google Scholar, 4Towle H.C. Kaytor E.N. Shih H.M. Annu. Rev. Nutr. 1997; 17: 405-433Crossref PubMed Scopus (248) Google Scholar). Although insulin and glucagon were long known as critical in regulating gene expression, it is only recently that carbohydrates also have been shown to play a key role in transcriptional regulation (3Girard J. Ferre P. Foufelle F. Annu. Rev. Nutr. 1997; 17: 325-352Crossref PubMed Scopus (302) Google Scholar, 4Towle H.C. Kaytor E.N. Shih H.M. Annu. Rev. Nutr. 1997; 17: 405-433Crossref PubMed Scopus (248) Google Scholar, 5Scott D.K. O'Doherty R.M. Stafford J.M. Newgard C.B. Granner D.K. J. Biol. Chem. 1998; 273: 24145-24151Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar). DNA sequences and DNA binding complexes involved in the glucose-regulated gene expression have been characterized recently in liver and β cells. In most glucose-sensitive tissues, glucose entry is mediated through specific glucose transporters; these include GLUT2, in the liver and β cells, and GLUT4, an insulin-sensitive transporter, in adipocytes and muscle (6Olson A.L. Pessin J.E. Annu. Rev. Nutr. 1996; 16: 235-256Crossref PubMed Scopus (382) Google Scholar). It seems likely that the main role of GLUT2 in gluconeogenic tissues, such as the liver, is to allow for a rapid equilibrium between intra- and extracellular glucose, in particular an easy secretion of glucose under gluconeogenic conditions. In hepatoma cells devoid of GLUT2 and cultured without glucose, the concentration of intracellular glucose 6-phosphate remains high, thus explaining the continuous stimulation of glucose-sensitive genes and consequent loss of glucose responsiveness (7Antoine B. Lefrançois-Martinez A.M. Le Guillou G. Leturque A. Vandewalle A. Kahn A. J. Biol. Chem. 1997; 272: 17937-17943Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). Accordingly, in GLUT2 −/− mice the intracellular glucose 6-phosphate concentration is high in fasting animals (8Guillam M.T. Burcelin R. Thorens B. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 12317-12321Crossref PubMed Scopus (99) Google Scholar, 9Burcelin R. del Carmen Munoz M. Guillam M.T. Thorens B. J. Biol. Chem. 2000; 275: 10930-10936Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar); and in patients with mutation in the GLUT2 gene (the Fanconi-Bickel syndrome), there is an associated accumulation of intrahepatic glycogen (10Santer R. Schneppenheim R. Dombrowski A. Gotze H. Steinmann B. Schaub J. Nat. Genet. 1997; 17: 324-326Crossref PubMed Scopus (234) Google Scholar). Transcription of the gene for L-PK is also abnormally stimulated in the liver of fasted GLUT2 −/− mice. Transfer of a GLUT2 transgene reestablishes a normal inhibition of glucose utilization by fasting and stimulation by carbohydrate feeding (9Burcelin R. del Carmen Munoz M. Guillam M.T. Thorens B. J. Biol. Chem. 2000; 275: 10930-10936Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar). Guillemain et al. (11Guillemain G. Loizeau M. Pincon-Raymond M. Girard J. Leturque A. J. Cell Sci. 2000; 113: 841-847PubMed Google Scholar) have recently suggested that the large intracytoplasmic loop of GLUT2 could also play the role of a signaling molecule. Indeed, hyperexpression of this loop in mhAT3F hepatoma cells (7Antoine B. Lefrançois-Martinez A.M. Le Guillou G. Leturque A. Vandewalle A. Kahn A. J. Biol. Chem. 1997; 272: 17937-17943Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar) abrogates glucose responsiveness. After its entry into liver, adipocytes, and β cells, glucose has to be metabolized to generate an intracellular signal that allows for transcriptional regulation of metabolic genes. Although it is now clear that the first step of glycolysis, namely phosphorylation of glucose to glucose 6-phosphate, is instrumental for glucose-dependent regulation (either positive or negative), the subsequent steps are still disputed and the exact nature of the active intermediate remains obscure (3Girard J. Ferre P. Foufelle F. Annu. Rev. Nutr. 1997; 17: 325-352Crossref PubMed Scopus (302) Google Scholar, 5Scott D.K. O'Doherty R.M. Stafford J.M. Newgard C.B. Granner D.K. J. Biol. Chem. 1998; 273: 24145-24151Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar). In the liver, glucose 6-phosphate can be used in glycolysis, the pentose phosphate pathway, glycogen synthesis, and hexosamine synthesis. Work from our laboratory using xylitol, an intermediate of the pentose phosphate pathway, has suggested that in hepatocytes in primary culture the glucose signal could be generated through the non-oxidative branch of the pentose phosphate pathway (12Doiron B. Cuif M.H. Chen R. Kahn A. J. Biol. Chem. 1996; 271: 5321-5324Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar). This result has been further extended in vivo by Massillonet al. (13Massillon D. Chen W. Barzilai N. Prus-Wertheimer D. Hawkins M. Liu R. Taub R. Rossetti L. J. Biol. Chem. 1998; 273: 228-234Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar), who noted that xylitol mimics the effect of hyperglycemia on glucose-regulated genes without a change in intracellular glucose 6-phosphate concentration in the liver. Alternatively, there are several reports suggesting that glucose 6-phosphate itself is a signaling molecule (3Girard J. Ferre P. Foufelle F. Annu. Rev. Nutr. 1997; 17: 325-352Crossref PubMed Scopus (302) Google Scholar, 14Goya L. de la Puente A. Ramos S. Martin M.A. Escriva F. Pascual-Leone A.M. J. Biol. Chem. 1999; 274: 24633-24640Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar). According to Mourrieras et al. (15Mourrieras F. Foufelle F. Foretz M. Morin J. Bouche S. Ferré P. Biochem. J. 1997; 326: 345-349Crossref PubMed Scopus (69) Google Scholar), only production of glucose 6-phosphate correlates accurately with the induction of glucose-regulated genes. Finally, for a specific subset of genes regulated by glucose through its metabolism in muscle and fat, the hexosamine biosynthetic pathway was reported to mediate the transcriptional effects of glucose on gene expression (16Sayeski P.P. Kudlow J.E. J. Biol. Chem. 1996; 271: 15237-15243Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar, 17Wang J. Liu R. Hawkins M. Barzilai N. Rossetti L. Nature. 1998; 393: 684-688Crossref PubMed Scopus (695) Google Scholar). It is likely that a phosphorylation/dephosphorylation cycle is involved in signaling the availability of glucose to the transcriptional machinery. In this regard, protein phosphatase inhibitors prevent the effects of glucose on L-PK gene expression 2B. Doiron, unpublished data. and other glucose-regulated genes (18Daniel S. Zhang S. DePaoli-Roach A.A. Kim K.H. J. Biol. Chem. 1996; 271: 14692-14697Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar, 19Foretz M. Carling D. Guichard C. Ferré P. Foufelle F. J. Biol. Chem. 1998; 273: 14767-14771Abstract Full Text Full Text PDF PubMed Scopus (214) Google Scholar, 20Datta U. Wexler I.D. Kerr D.S. Raz I. Patel M.S. Biochim. Biophys. Acta. 1999; 1447: 236-243Crossref PubMed Scopus (17) Google Scholar). The involvement of the cAMP-dependent protein kinase in regulating the glucose-dependent signaling pathway is well documented (4Towle H.C. Kaytor E.N. Shih H.M. Annu. Rev. Nutr. 1997; 17: 405-433Crossref PubMed Scopus (248) Google Scholar,21Viollet B. Kahn A. Raymondjean M. Mol. Cell. Biol. 1997; 17: 4208-4219Crossref PubMed Scopus (148) Google Scholar, 22Gourdon L. Lou D.Q. Raymondjean M. Vasseur-Cognet M. Kahn A. FEBS Lett. 1999; 459: 9-14Crossref PubMed Scopus (17) Google Scholar). More recently, another protein kinase, the AMP-activated protein kinase (AMPK), has been suggested to play a key role in transmission of the glucose signal for transcription. AMPK is a serine/threonine kinase acting as a key metabolic “master switch” by phosphorylating target proteins involved in carbohydrate and fat metabolism in response to changes in cellular energy charge. AMPK is activated by stresses that deplete ATP, leading to a rise in the AMP/ATP ratio within the cell (23Hardie D.G. Carling D. Carlson M. Annu. Rev. Biochem. 1998; 67: 821-855Crossref PubMed Scopus (1270) Google Scholar). AMPK is a heterotrimeric complex of a catalytic (α) and two regulatory subunit (β and γ) proteins. Proteins related to all three subunits have been characterized in the yeast Snf1p complex (24Carlson M. Curr. Opin. Genet. Dev. 1998; 8: 560-564Crossref PubMed Scopus (72) Google Scholar). There are two catalytic subunit isoforms encoded by two different genes, namely α1 and α2 (23Hardie D.G. Carling D. Carlson M. Annu. Rev. Biochem. 1998; 67: 821-855Crossref PubMed Scopus (1270) Google Scholar). Interestingly, although α1-containing complexes are exclusively cytoplasmic, α2 complexes are found both in the nucleus and cytoplasm (25Salt I. Celler J.W. Hawley S.A. Prescott A. Woods A. Carling D. Hardie D.G. Biochem. J. 1998; 334: 177-187Crossref PubMed Scopus (376) Google Scholar, 26da Silva Xavier G. Leclerc I. Salt I.P. Doiron B. Hardie D.G. Kahn A. Rutter G.A. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 4023-4028Crossref PubMed Scopus (187) Google Scholar). AMPK activity was first reported to be decreased in β cell lines incubated in elevated glucose concentrations (26da Silva Xavier G. Leclerc I. Salt I.P. Doiron B. Hardie D.G. Kahn A. Rutter G.A. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 4023-4028Crossref PubMed Scopus (187) Google Scholar, 27Salt I.P. Johnson G. Ashcroft S.J.H. Hardie D.G. Biochem. J. 1998; 335: 533-539Crossref PubMed Scopus (336) Google Scholar). We and others have shown that the AMPK activator, 5-amino-4-imidazolecarboxamide riboside, inhibits the glucose-dependent activation of several genes in hepatocytes in primary culture (19Foretz M. Carling D. Guichard C. Ferré P. Foufelle F. J. Biol. Chem. 1998; 273: 14767-14771Abstract Full Text Full Text PDF PubMed Scopus (214) Google Scholar, 28Leclerc I. Kahn A. Doiron B. FEBS Lett. 1998; 431: 180-184Crossref PubMed Scopus (128) Google Scholar). Thus, inactivation of AMPK may restore the transcriptional activity of glucose-responsive genes. To test this hypothesis, the group of Rutter in collaboration with our laboratory (26da Silva Xavier G. Leclerc I. Salt I.P. Doiron B. Hardie D.G. Kahn A. Rutter G.A. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 4023-4028Crossref PubMed Scopus (187) Google Scholar) used the single-cell antibody microinjection strategy, coupled with dynamic imaging of that microinjection of the α1 AMPK catalytic mimics the effects of elevated glucose on the L-PK and in β cells. Interestingly, in the effects were only antibody was both in the nucleus and the the of a phosphorylation the of the α2 with 5-amino-4-imidazolecarboxamide the effect of glucose on (26da Silva Xavier G. Leclerc I. Salt I.P. Doiron B. Hardie D.G. Kahn A. Rutter G.A. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 4023-4028Crossref PubMed Scopus (187) Google Scholar). that changes in AMPK activity are and for the regulation of the L-PK gene by this and that play an important role in the regulation of the gene This result is of with to is known In the kinase complex is activated by glucose which in inactivation of involved in gene such as M. Trends Genet. 1999; 15: 29-33Abstract Full Text Full Text PDF PubMed Scopus (318) Google Scholar, M. Curr. Opin. Genet. Dev. 1998; 8: 560-564Crossref PubMed Scopus (72) Google Scholar). In cells, AMPK seems to have the effect on gene of a AMPK inhibits an or a of AMPK are in our and the of AMPK mice is in To the effect of glucose on gene our laboratory has the regulation of the L-PK gene expression by We a DNA for the positive response to glucose vivo vivo N. Raymondjean M. Kahn A. PubMed Scopus Google Scholar, M.H. A. Kahn A. S. J. Biol. Chem. Full Text PDF PubMed Google Scholar, A. Cuif M.H. Kahn A. Raymondjean M. Mol. Cell. Biol. PubMed Scopus Google Scholar, A.M. A. B. Raymondjean M. Kahn A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). This the glucose response element is related to the carbohydrate response element by the group of H.M. H.C. J. Biol. Chem. Full Text PDF PubMed Google Scholar, Liu H.C. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) in the regulatory of the has been recently in the of the gene for the glucagon L. B. M. J. M. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar). The complex that to the of the L-PK and genes with an DNA binding the to glucose responsiveness N. Raymondjean M. Kahn A. PubMed Scopus Google Scholar, A. Cuif M.H. Kahn A. Raymondjean M. Mol. Cell. Biol. PubMed Scopus Google Scholar, Liu H.C. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). sequences in of a are in of the to the carbohydrate response N. Raymondjean M. Kahn A. PubMed Scopus Google Scholar, A. Cuif M.H. Kahn A. Raymondjean M. Mol. Cell. Biol. PubMed Scopus Google Scholar, Liu H.C. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The L-PK of two by the upstream stimulatory which are of the A. Cuif M.H. Kahn A. Raymondjean M. Mol. Cell. Biol. PubMed Scopus Google Scholar, Liu H.C. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). We have shown that in the liver, as well as in most binding activity is mainly for by the B. A.M. A. Kahn A. Raymondjean M. A. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar). using cells and gene mice that the are important for a normal activation of genes by glucose A.M. A. B. Raymondjean M. Kahn A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, A.A. D. M. Raymondjean M. Kahn A. S. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar, M. A.A. D. Raymondjean M. Kahn A. S. J. Biol. 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Source: Journal of Biological Chemistry
Institutions: Inserm, Institut Cochin, Université Paris Descartes
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W2116233022