|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 275, Issue 41, 31555-31558, October 13, 2000
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Institut Cochin de Génétique
Moléculaire, U.129 INSERM, Université René Descartes,
75014 Paris, France
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. 1). 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 In most glucose-sensitive tissues, glucose entry is mediated
through specific glucose transporters; these include GLUT2, in the
liver and Guillemain et al. (11) 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 (7) abrogates glucose responsiveness.
After its entry into liver, adipocytes, and 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
expression2 and other
glucose-regulated genes (18-20). The involvement of the
cAMP-dependent protein kinase in regulating the
glucose-dependent signaling pathway is well documented (4,
21, 22). 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 (23). AMPK is a heterotrimeric complex of
a catalytic ( AMPK activity was first reported to be decreased in To assess the effect of glucose on gene transcription, our
laboratory has extensively studied the regulation of the rat L-PK gene
expression by glucose. We defined a DNA sequence responsible for
mediating the positive response to glucose ex vivo and
in vivo (29-32). This sequence, termed the glucose response
element (GlRE), is closely related to the carbohydrate response element (ChoRE) described by the group of Towle (33, 34) in the regulatory region of the S14 gene. A similar glucose-activatable region has been
recently identified in the promoter of the gene for the glucagon receptor (35). The complex that binds to the GlRE/ChoRE of the L-PK and
S14 genes cooperates with an adjacent DNA binding site, termed the
auxiliary site, to confer strong glucose responsiveness (29, 31, 34).
However, oligomerized GlRE/ChoRE sequences placed in front of a
heterologous promoter are sufficient, in absence of the auxiliary site,
to confer the carbohydrate response (29, 31, 34).
The L-PK GlRE consists of two palindromic non-canonical E boxes
(CANNTG) separated by 5 base pairs. These E boxes bind the upstream
stimulatory factors (USFs), which are members of the basic
helix-loop-helix leucine zipper family (31, 34). We have shown that in
the liver, as well as in most tissues tested, USF binding activity is
mainly accounted for by the USF1/USF2 heterodimer (36). Our results
using cells and gene knock-out mice indicate that the endogenous USFs
are important for a kinetically normal activation of various
diet-dependent genes by glucose (32, 37-39). However,
these factors cannot, by themselves, explain the transcriptional
regulation of glucose-responsive genes by glucose. Indeed, most genes
whose promoters include USF-binding E boxes are not regulated by
glucose. In addition, the glucose responsiveness conferred by
GlREs/ChoREs is not parallel to their affinity for USFs (40). Finally,
USF synthesis as well as DNA binding activity do not appear to be
regulated by the diet. We therefore sought novel partners of the
glucose response complex using the one-hybrid system in yeast. We
identified, in addition to USF, chicken ovalbumin upstream
promoter-transcription factor II (COUP-TFII), an orphan nuclear
receptor of the steroid/thyroid hormone receptor superfamily. COUP-TFII
binds to the GlRE in vitro, and COUP-TF-containing complexes that interact with the GlRE are present in liver nuclear extracts (41).
The COUP-TF and USF binding sites are overlapping, and binding
of one factor interferes with binding of the other. Consequently, overexpression of COUP-TFII inhibits USF-dependent
transactivation of the L-PK gene promoter and also represses its
stimulation by glucose in hepatocytes in primary culture. Furthermore,
a mutated GlRE binding site with very low affinity for COUP-TFII
impaired the glucose response because of increased activity under low
glucose conditions (41). We propose that COUP-TFII-containing dimers are involved in a glucose sensor system abrogating transactivation by
USFs in the absence of glucose. This sensor complex could be regulated
by interaction with other partner(s) sensitive to glucose, that we are
currently looking for.
There are several recent reports concerning GlRE DNA-binding
proteins. Hasegawa et al. (42) reported that carbohydrate
refeeding resulted in an increase in the concentration of a novel L-PK
GlRE binding activity in the liver. They excluded USF, Sp1, c-Myc, and
HNF4 as being involved in this activity. So far, the cognate DNA-binding proteins have not been purified. Yamada et al.
(43) described the purification of two novel GlRE-binding proteins that
may be related to COUP-TFII. Finally, Koo and Towle (44) have recently
characterized a new ChoRE binding activity that correlates with
glucose-dependent transcriptional activity. This DNA
binding activity is only recovered with oligonucleotides capable of
conferring a glucose response and not with mutants of the sites that
are inactive in supporting the glucose response. This binding activity
does not seem to be regulated by dietary glucose. The authors proposed
a new model for the ChoRE consisting of two E box half-sites related to
CACG motifs.
Recently, the sterol response element-binding protein 1c (SREBP-1c)
(45, 46) was also proposed as a mediator of glucose induction of genes
encoding proteins of glycolytic and lipogenic pathways, including L-PK
and S14 genes (47). However, this effect of SREBP-1c on
glucose-responsive genes is likely to reflect the role of SREBP-1c as a
mediator of insulin action (as discussed in detail in the third
minireview of this series by Osborne (81)) rather than its direct
involvement in the glucose signaling pathway. Indeed, the L-PK GlRE has
a very low affinity for SREBP (44), which is, in addition, a very poor
transactivator of the L-PK gene promoter (48, 49). Accordingly,
complete SREBP-1 deficiency in knock-out mice results only in a partial
abrogation of L-PK gene expression in response to carbohydrate
refeeding, whereas insulin-responsive genes such as glucose-6-phosphate
dehydrogenase and glycerol 3-phosphate acyltransferase are totally
unresponsive (50). In fact, the impaired glucose response of the L-PK
gene in the liver of SREBP1 A summary of the role of glucose and insulin in the transcriptional
regulation of glycolytic and lipogenic genes in the liver is presented
in Fig. 2.
Several reports have suggested that the ubiquitously expressed
transcription factor Sp1 may also provide a mechanism for glucose responsiveness. This was first reported for the ACC gene in adipocytes where glucose was able to induce an increase of Sp1 binding activity (52). This induction was not due to an increase in the amount of Sp1
but to dephosphorylation of the existing Sp1 in the nucleus. Glucose
treatment increases the amount of protein phosphatase 1 catalytic
subunit resulting in the activation of Sp1 binding activity on the ACC
promoter (18). A glucose-dependent Sp1 dephosphorylation resulting in a higher DNA binding activity has been confirmed (53).
Members of the Sp1 family have also been proposed to be required for
glucose-dependent induction of the plasminogen activator inhibitor 1 gene (54) and the transforming growth factor An impressive breakthrough in the field of gene regulation by
glucose involves the control of the insulin gene promoter by the
transcription factor pancreatic duodenum
homeobox protein, PDX1 (IPF-1/STF-1/IUF-1/IDX-1), in
pancreatic The pivotal role of PDX1 in the nutrient regulation of insulin mRNA
production was further assessed using pancreatic Other glucose-dependent genes, such as the L-PK (26,
74), are also regulated in There are clearly different mechanisms of gene activation in
mammalian tissues induced by dietary carbohydrate. Some genes are
mainly activated by insulin, whose secretion is increased by glucose;
this is the case for SREBP1 and glucokinase in the liver (Fig. 2) and
may also be true for the proinsulin gene in Other genes are regulated by glucose itself in the presence of
glucose-phosphorylating enzymes, namely glucokinase, where the role of
AMPK has been demonstrated in both the liver and *
This minireview will be reprinted
in the 2000 Minireview Compendium, which
will be available in December, 2000. This is the second article of three in the
"Nutrient Control of Gene Transcription Minireview Series."
Published, JBC Papers in Press, August 8, 2000, DOI 10.1074/jbc.R000016200
2
B. Doiron, unpublished data.
The abbreviations used are:
L-PK, L-type
pyruvate kinase;
ACC, acetyl-CoA carboxylase;
S14, spot 14;
AMPK, AMP-activated protein kinase;
GlRE, glucose response element;
ChoRE, carbohydrate response element;
COUP-TF, chicken ovalbumin upstream
promoter-transcription factor;
USF, upstream stimulatory factor;
SREBP, sterol response element-binding protein;
PI3K, phosphatidylinositol
3-kinase;
PDX1, pancreatic duodenum homeobox 1.
MINIREVIEW
Glucose Regulation of Gene Transcription*
,
INTRODUCTION
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. 2-4). 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 (3-5). DNA sequences and DNA
binding complexes involved in the glucose-regulated gene expression
have been characterized recently in liver and cells.
The Glucose Signaling Pathway
cells, and GLUT4, an insulin-sensitive transporter, in
adipocytes and muscle (6). 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 (7). Accordingly, in GLUT2 
/ mice the
intracellular glucose 6-phosphate concentration is high in fasting
animals (8, 9); and in patients with mutation in the GLUT2 gene (the
Fanconi-Bickel syndrome), there is an associated accumulation of
intrahepatic glycogen (10). 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
(9).
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 (3, 5). 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 (12).
This result has been further extended in vivo by Massillon
et al. (13), 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 (3, 14). According to
Mourrieras et al. (15), 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 (16, 17).
Kinase Cascade and Role of AMPK
) and two regulatory subunit ( and 
) proteins. Proteins related to all three subunits have been characterized in the
yeast Snf1p complex (24). There are two catalytic subunit isoforms
encoded by two different genes, namely 1 and 2 (23). Interestingly, although 1-containing complexes are exclusively cytoplasmic, 2 complexes are found both in the nucleus and cytoplasm (25, 26).
cell lines
incubated in elevated glucose concentrations (26, 27). 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 (19, 28). 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 (26) used the single-cell antibody
microinjection strategy, coupled with dynamic imaging of luciferase
reporter constructs. These studies demonstrated that microinjection of antibodies against 2, but not the 1 AMPK catalytic subunit, mimics the effects of elevated glucose on the L-PK and preproinsulin promoters in MIN6 cells. Interestingly, in each case the effects were only observed when antibody injection was performed both in the
nucleus and the cytosol, indicating the importance of either a
cytosolic phosphorylation event and/or the subcellular localization of
the 2 subunits. Incubation with 5-amino-4-imidazolecarboxamide riboside diminished, but did not abolish, the effect of glucose on
preproinsulin transcription (26). These data suggest that glucose-induced changes in AMPK activity are necessary and sufficient for the regulation of the L-PK gene by this sugar (see Fig. 1) and that
they play an important role in the regulation of the preproinsulin gene
promoter. This result is of interest with regard to what is known about
yeast. In Saccharomyces cerevisiae, the Snfp kinase complex
is activated by glucose removal, which results in
phosphorylation-dependent inactivation of transcription
factors involved in gene repression, such as Mig1 (1, 24). In mammalian cells, AMPK seems to have the opposite effect on gene expression; instead of inhibiting a repressor, AMPK inhibits an activator or
activates a repressor (Fig. 1). Possible
targets of AMPK are currently being investigated in our laboratory, and
the generation of AMPK knock-out mice is in progress.
View larger version (16K):
[in a new window]
Fig. 1.
Role of AMPK in the regulation by glucose of
the L-PK gene transcription in pancreatic cell. When cultured under low glucose conditions, AMPK
activity is elevated and L-PK gene transcription is low. AMPK activity
is inhibited by an elevated glucose concentration leading to an
increase in L-PK gene transcription. Microinjection of antibodies to
the 2 subunit of AMPK mimics the effects of elevated
glucose on the L-PK promoter activity (26).
The Glucose Response Elements of L-PK and S14
Genes
Other Putative Partners of the GlRE/ChoRE of L-PK and
S14
/ mice could result from the deficiency in glucokinase, the gene transcription of which is
insulin/SREBP-1c-dependent (51). Indeed, glucokinase
induction by insulin/SREBP-1c is needed for glucose phosphorylation to
glucose 6-phosphate, an indispensable intermediate of
glucose-dependent gene activation.
View larger version (36K):
[in a new window]
Fig. 2.
Role of glucose and insulin in the
transcriptional regulation of glycolytic and lipogenic genes in the
liver. The involvement of the PI3K/protein kinase B
(PKB) pathway in the insulin-dependent
activation of the glucokinase gene transcription has been demonstrated
recently (80). An overview of the functional DNA element ( 144 to
172 base pairs from the start site of transcription of the rat L-PK
gene) involved in the glucose-dependent regulation of the
L-PK gene transcription is presented. The E boxes and direct repeat
(DR1 and DR7) elements in the GlRE are indicated.
PPP, pentose phosphate pathway.
Transcriptional Factors of the Sp1 Family Are
Involved in Glucose Responsiveness
(16) gene
through the glucosamine pathway in vascular muscle cells. Finally,
factors of the Sp1 family were reported to be somehow involved in
regulation of glucose/insulin-dependent genes encoding leptin, fatty acid synthase, and ATP citrate-lyase (55, 56). In the
case of ATP citrate-lyase, the level of expression of Sp1 and Sp3
factors was reported to be directly regulated by glucose (57). It is
interesting to note that in the absence of adequate nutrition, Sp1
becomes hypoglycosylated and thereby subject to proteolytic degradation
(58).
Transcriptional Regulation of Insulin Gene Expression
in Pancreatic
Cells: Role of PDX1 cells. PDX1 was first described as a key factor for
lineage determination of the developing endocrine pancreas (59, 60).
Strong evidence now supports a role for this homeodomain transcription
factor in the mechanism whereby glucose stimulates insulin gene
transcription in cells. Increased glucose concentration in the
mature islet leads to PDX1 phosphorylation and subsequent translocation
into the nucleus, where it binds to the insulin gene promoter resulting in its transcriptional activation (61, 62).
Glucose-dependent activation of PDX1 nuclear translocation
occurs through a cell signaling pathway involving PI3K. Today,
involvement of p38/SAPK2 in the downstream pathway is disputed (62,
63). Other metabolizable nutrients that induce insulin release
(including fructose, pyruvate, and xylitol), as well as insulin itself,
were also shown to activate PDX1 DNA binding activity and insulin
promoter activity through PI3K (64). Further experiments are now needed
to determine whether the effects of insulin and glucose are additive or
whether glucose acts as an insulin secretagogue, whereas PDX1 and
proinsulin gene activation are triggered by insulin (65). A schematic
view of glucose and insulin regulation of PDX1 DNA binding and insulin gene promoter activity is presented in Fig.
3.
View larger version (37K):
[in a new window]
Fig. 3.
Role of glucose and insulin in the
stimulation of PDX1 DNA binding activity and insulin gene transcription
in the pancreatic cell. Both insulin and
glucose were shown to activate insulin gene transcription via a pathway
involving PI3K and stress-activated protein kinase 2 (SAPK2)
(64). However, whether glucose is able to activate PI3K independently
of stimulating insulin secretion has not been determined.
cell lines. These
studies showed that impaired glucose-regulated insulin secretion and
insulin content are associated with dysregulated PDX1 expression (66,
67). The role of PDX1 in diabetes has been increasingly documented over
the past several years. A dominant negative mutation in PDX1 was shown
to cause maturity-onset diabetes of the young; MODY4 is an autosomal
dominant form of type 2 diabetes characterized by an early onset and a
primary defect of insulin secretion (68, 69). Furthermore, new
mutations in PDX1 that may predispose to type 2 diabetes in humans were
reported, their phenotype depending upon the nature of the mutation
(70, 71). Very recently, Ferber et al. (72, 73) have
demonstrated that in vivo transduction of hepatocytes with a
recombinant adenovirus-PDX1 vector reactivates the silent proinsulin
gene, as well as genes for proconvertases PC1/PC3; this reinforces the
view that PDX1 is a major transactivator of cell-specific genes.
cells, and the mechanisms underlying their regulation are under investigation. Recently, Josefsen et al. (75) using a subtraction cloning strategy isolated the zinc finger transcription factor Egr-1 and demonstrated that its expression is up-regulated in primary islet cells in response to glucose. In view
of the close homology of Egr-1 with transcription factors that regulate
carbohydrate metabolism in yeast, the authors propose that Egr-1 might
play a pivotal role in response to sustained glucose stimulation. The
genes regulated by Egr-1 in cells are currently unknown.
Conclusions
cells. Hepatic SREBP1
and PDX1 in cells appear to be major insulin-dependent
transactivators of gene transcription. Some genes are also inhibited by
insulin and the role of different winged helix transcription factors or
forkhead; a family of transcription factors such as FKHR has been well
documented recently (76-78). The insulin signaling pathways, mediating
either positive or negative effects on the transcriptional machinery,
mainly pass through PI3K activation (79, 80).
cells. However,
the transcription factors involved in the glucose response differ
according to the regulated genes and currently remain elusive. In fact,
it is probable that there is no single regulator of gene expression by
glucose but rather that glucose-dependent cues allow the
cross-talk between factors and most likely regulatory co-factors to
determine the transcriptional activation in a cell-specific manner. The
specificity of the response could be achieved through post-translational modifications, mainly phosphorylation of various tissue-specific or ubiquitous factors. Nuclear translocation, as
exemplified for PDX1 in cells and Mig1 in yeast, offers an additional level of regulation. Alternatively, the concentration of
transcription factors could be directly regulated by glucose. We
predict that progress in deciphering the mechanisms of
glucose-dependent gene regulation will quickly follow those
made in the last several years for insulin control of gene transcription.
FOOTNOTES
To whom correspondence should be addressed: ICGM, INSERM U.129,
24, rue du Faubourg Saint-Jacques, 75014 Paris, France. Tel.: 33-1-44-41-24-08; Fax: 33-1-44-41-24-21; E-mail: vaulont@cochin. inserm.fr.
ABBREVIATIONS
REFERENCES
1.
Johnston, M.
(1999)
Trends Genet.
15,
29-33
2.
Vaulont, S.,
and Kahn, A.
(1994)
FASEB J.
8,
28-35
3.
Girard, J.,
Ferre, P.,
and Foufelle, F.
(1997)
Annu. Rev. Nutr.
17,
325-352
4.
Towle, H. C.,
Kaytor, E. N.,
and Shih, H. M.
(1997)
Annu. Rev. Nutr.
17,
405-433
5.
Scott, D. K.,
O'Doherty, R. M.,
Stafford, J. M.,
Newgard, C. B.,
and Granner, D. K.
(1998)
J. Biol. Chem.
273,
24145-24151
6.
Olson, A. L.,
and Pessin, J. E.
(1996)
Annu. Rev. Nutr.
16,
235-256
7.
Antoine, B.,
Lefrançois-Martinez, A. M.,
Le Guillou, G.,
Leturque, A.,
Vandewalle, A.,
and Kahn, A.
(1997)
J. Biol. Chem.
272,
17937-17943
8.
Guillam, M. T.,
Burcelin, R.,
and Thorens, B.
(1998)
Proc. Natl. Acad. Sci. U. S. A.
95,
12317-12321
9.
Burcelin, R.,
del Carmen Munoz, M.,
Guillam, M. T.,
and Thorens, B.
(2000)
J. Biol. Chem.
275,
10930-10936
10.
Santer, R.,
Schneppenheim, R.,
Dombrowski, A.,
Gotze, H.,
Steinmann, B.,
and Schaub, J.
(1997)
Nat. Genet.
17,
324-326
11.
Guillemain, G.,
Loizeau, M.,
Pincon-Raymond, M.,
Girard, J.,
and Leturque, A.
(2000)
J. Cell Sci.
113,
841-847
12.
Doiron, B.,
Cuif, M. H.,
Chen, R.,
and Kahn, A.
(1996)
J. Biol. Chem.
271,
5321-5324
13.
Massillon, D.,
Chen, W.,
Barzilai, N.,
Prus-Wertheimer, D.,
Hawkins, M.,
Liu, R.,
Taub, R.,
and Rossetti, L.
(1998)
J. Biol. Chem.
273,
228-234
14.
Goya, L.,
de la Puente, A.,
Ramos, S.,
Martin, M. A.,
Escriva, F.,
and Pascual-Leone, A. M.
(1999)
J. Biol. Chem.
274,
24633-24640
15.
Mourrieras, F.,
Foufelle, F.,
Foretz, M.,
Morin, J.,
Bouche, S.,
and Ferré, P.
(1997)
Biochem. J.
326,
345-349
16.
Sayeski, P. P.,
and Kudlow, J. E.
(1996)
J. Biol. Chem.
271,
15237-15243
17.
Wang, J.,
Liu, R.,
Hawkins, M.,
Barzilai, N.,
and Rossetti, L.
(1998)
Nature
393,
684-688
18.
Daniel, S.,
Zhang, S.,
DePaoli-Roach, A. A.,
and Kim, K. H.
(1996)
J. Biol. Chem.
271,
14692-14697
19.
Foretz, M.,
Carling, D.,
Guichard, C.,
Ferré, P.,
and Foufelle, F.
(1998)
J. Biol. Chem.
273,
14767-14771
20.
Datta, U.,
Wexler, I. D.,
Kerr, D. S.,
Raz, I.,
and Patel, M. S.
(1999)
Biochim. Biophys. Acta
1447,
236-243
21.
Viollet, B.,
Kahn, A.,
and Raymondjean, M.
(1997)
Mol. Cell. Biol.
17,
4208-4219
22.
Gourdon, L.,
Lou, D. Q.,
Raymondjean, M.,
Vasseur-Cognet, M.,
and Kahn, A.
(1999)
FEBS Lett.
459,
9-14
23.
Hardie, D. G.,
Carling, D.,
and Carlson, M.
(1998)
Annu. Rev. Biochem.
67,
821-855
24.
Carlson, M.
(1998)
Curr. Opin. Genet. Dev.
8,
560-564
25.
Salt, I.,
Celler, J. W.,
Hawley, S. A.,
Prescott, A.,
Woods, A.,
Carling, D.,
and Hardie, D. G.
(1998)
Biochem. J.
334,
177-187
26.
da Silva Xavier, G.,
Leclerc, I.,
Salt, I. P.,
Doiron, B.,
Hardie, D. G.,
Kahn, A.,
and Rutter, G. A.
(2000)
Proc. Natl. Acad. Sci. U. S. A.
97,
4023-4028
27.
Salt, I. P.,
Johnson, G.,
Ashcroft, S. J. H.,
and Hardie, D. G.
(1998)
Biochem. J.
335,
533-539
28.
Leclerc, I.,
Kahn, A.,
and Doiron, B.
(1998)
FEBS Lett.
431,
180-184
29.
Bergot, M. O.,
Diaz-Guerra, M. J.,
Puzenat, N.,
Raymondjean, M.,
and Kahn, A.
(1992)
Nucleic Acids Res.
20,
1871-1877
30.
Cuif, M. H.,
Porteu, A.,
Kahn, A.,
and Vaulont, S.
(1993)
J. Biol. Chem.
268,
13769-13772
31.
Diaz-Guerra, M. J.,
Bergot, M. O.,
Martinez, A.,
Cuif, M. H.,
Kahn, A.,
and Raymondjean, M.
(1993)
Mol. Cell. Biol.
13,
7725-7733
32.
Lefrancois-Martinez, A. M.,
Martinez, A.,
Antoine, B.,
Raymondjean, M.,
and Kahn, A.
(1995)
J. Biol. Chem.
270,
2640-2643
33.
Shih, H. M.,
and Towle, H. C.
(1992)
J. Biol. Chem.
267,
13222-13228
34.
Shih, H.-M.,
Liu, Z.,
and Towle, H. C.
(1995)
J. Biol. Chem.
270,
21991-21997
35.
Portois, L.,
Maget, B.,
Tastenoy, M.,
Perret, J.,
and Svoboda, M.
(1999)
J. Biol. Chem.
274,
8181-8190
36.
Viollet, B.,
Lefrancois-Martinez, A. M.,
Henrion, A.,
Kahn, A.,
Raymondjean, M.,
and Martinez, A.
(1996)
J. Biol. Chem.
271,
1405-1415
37.
Vallet, V. S.,
Henrion, A. A.,
Bucchini, D.,
Casado, M.,
Raymondjean, M.,
Kahn, A.,
and Vaulont, S.
(1997)
J. Biol. Chem.
272,
21944-21949
38.
Vallet, V. S.,
Casado, M.,
Henrion, A. A.,
Bucchini, D.,
Raymondjean, M.,
Kahn, A.,
and Vaulont, S.
(1998)
J. Biol. Chem.
273,
20175-20179
39.
Casado, M.,
Vallet, V.,
Kahn, A.,
and Vaulont, S.
(1999)
J. Biol. Chem.
274,
2009-2013
40.
Kaytor, E. N.,
Shih, H.,
and Towle, H. C.
(1997)
J. Biol. Chem.
272,
7525-7531
41.
Lou, D. Q.,
Tannour, M.,
Selig, L.,
Thomas, D.,
Kahn, A.,
and Vasseur-Cognet, M.
(1999)
J. Biol. Chem.
274,
28385-28394
42.
Hasegawa, J. I.,
Osatomi, K.,
Wu, R. F.,
and Uyeda, K.
(1999)
J. Biol. Chem.
274,
1100-1107
43.
Yamada, K.,
Tanaka, T.,
and Noguchi, T.
(1999)
Biochem. Cell Biol.
257,
44-49
44.
Koo, S. H.,
and Towle, H. C.
(2000)
J. Biol. Chem.
275,
5200-5207
45.
Tontonoz, P.,
Kim, J. B.,
Graves, R. A.,
and Spiegelman, B. M.
(1993)
Mol. Cell. Biol.
13,
4753-4759
46.
Yokoyama, C.,
Wang, X.,
Briggs, M. R.,
Admon, A.,
Wu, J.,
Hua, X.,
Goldstein, J. L.,
and Brown, M. S.
(1993)
Cell
75,
187-197
47.
Foretz, M.,
Pacot, C.,
Dugail, I.,
Lemarchand, P.,
Guichard, C.,
Le Liepvre, X.,
Berthelier-Lubrano, C.,
Spiegelman, B.,
Kim, J. B.,
Ferre, P.,
and Foufelle, F.
(1999)
Mol. Cell. Biol.
19,
3760-3768
48.
Mater, M. K.,
Thelen, A. P.,
Pan, D. A.,
and Jump, D. B.
(1999)
J. Biol. Chem.
274,
32725-32732
49.
Moriizumi, S.,
Gourdon, L.,
Lefrancois-Martinez, A. M.,
Kahn, A.,
and Raymondjean, M.
(1998)
Gene Expr.
7,
103-113
50.
Shimano, H.,
Yahagi, N.,
Amemiya-Kudo, M.,
Hasty, A. H.,
Osuga, J.,
Tamura, Y.,
Shionoiri, F.,
Iizuka, Y.,
Ohashi, K.,
Harada, K.,
Gotoda, T.,
Ishibashi, S.,
and Yamada, N.
(1999)
J. Biol. Chem.
274,
35832-35839
51.
Foretz, M.,
Guichard, C.,
Ferre, P.,
and Foufelle, F.
(1999)
Proc. Natl. Acad. Sci. U. S. A.
96,
12737-12742
52.
Daniel, S.,
and Kim, K. H.
(1996)
J. Biol. Chem.
271,
1385-1392
53.
Schafer, D.,
Hamm-Kunzelmann, B.,
and Brand, K.
(1997)
FEBS Lett.
417,
325-328
54.
Chen, Y. Q.,
Su, M.,
Walia, R. R.,
Hao, Q.,
Covington, J. W.,
and Vaughan, D. E.
(1998)
J. Biol. Chem.
273,
8225-8231
55.
Fukuda, H.,
Noguchi, T.,
and Iritani, N.
(1999)
FEBS Lett.
464,
113-117
56.
Fukuda, H.,
and Iritani, N.
(1999)
FEBS Lett.
455,
165-169
57.
Moon, Y. A.,
Kim, K. S.,
Cho, U. H.,
Yoon, D. J.,
and Park, S. W.
(1999)
Exp. Mol. Med.
31,
108-114
58.
Han, I.,
and Kudlow, J. E.
(1997)
Mol. Cell. Biol.
17,
2550-2558
59.
Guz, Y.,
Montminy, M. R.,
Stein, R.,
Leonard, J.,
Gamer, L. W.,
Wright, C. V.,
and Teitelman, G.
(1995)
Development
121,
11-18
60.
Jonsson, J.,
Carlsson, L.,
Edlund, T.,
and Edlund, H.
(1994)
Nature
371,
606-609
61.
Rafiq, I.,
Kennedy, H. J.,
and Rutter, G. A.
(1998)
J. Biol. Chem.
273,
23241-23247
62.
Macfarlane, W. M.,
McKinnon, C. M.,
Felton-Edkins, Z. A.,
Cragg, H.,
James, R. F. L.,
and Docherty, K.
(1999)
J. Biol. Chem.
274,
1011-1016
63.
Rafiq, I.,
da Silva Xavier, G.,
Hooper, S.,
and Rutter, G. A.
(2000)
J. Biol. Chem.
275,
15977-15984
64.
Wu, H.,
MacFarlane, W. M.,
Tadayyon, M.,
Arch, J. R.,
James, R. F.,
and Docherty, K.
(1999)
Biochem. J.
344,
813-818
65.
Leibiger, I. B.,
Leibiger, B.,
Moede, T.,
and Berggren, P. O.
(1998)
Mol. Cell
1,
933-938
66.
MacFarlane, W. M.,
Chapman, J. C.,
Shepherd, R. M.,
Hashmi, M. N.,
Kamimura, N.,
Cosgrove, K. E.,
O'Brien, R. E.,
Barnes, P. D.,
Hart, A. W.,
Docherty, H. M.,
Lindley, K. J.,
Aynsley-Green, A.,
James, R. F.,
Docherty, K.,
and Dunne, M. J.
(1999)
J. Biol. Chem.
274,
34059-34066
67.
Seijffers, R.,
Ben-David, O.,
Cohen, Y.,
Karasik, A.,
Berezin, M.,
Newgard, C. B.,
and Ferber, S.
(1999)
Endocrinology
140,
3311-3317
68.
Stoffers, D. A.,
Ferrer, J.,
Clarke, W. L.,
and Habener, J. F.
(1997)
Nat. Genet.
17,
138-139
69.
Stoffers, D. A.,
Stanojevic, V.,
and Habener, J. F.
(1998)
J. Clin. Invest.
102,
232-241
70.
Hani, E. H.,
Stoffers, D. A.,
Chevre, J. C.,
Durand, E.,
Stanojevic, V.,
Dina, C.,
Habener, J. F.,
and Froguel, P.
(1999)
J. Clin. Invest.
104,
41-48
71.
Macfarlane, W. M.,
Frayling, T. M.,
Ellard, S.,
Evans, J. C.,
Allen, L. I.,
Bulman, M. P.,
Ayres, S.,
Shepherd, M.,
Clark, P.,
Millward, A.,
Demaine, A.,
Wilkin, T.,
Docherty, K.,
and Hattersley, A. T.
(1999)
J. Clin. Invest.
104,
33-39
72.
Ferber, S.,
Halkin, A.,
Cohen, H.,
Ber, I.,
Einav, Y.,
Goldberg, I.,
Barshack, I.,
Seijffers, R.,
Kopolovic, J.,
Kaiser, N.,
and Karasik, A.
(2000)
Nat. Med
6,
568-572
73.
Kahn, A.
(2000)
Nat. Med.
6,
505-506
74.
Marie, S.,
Diaz-Guerra, M. J.,
Miquerol, L.,
Kahn, A.,
and Iynedjian, P. B.
(1993)
J. Biol. Chem.
268,
23881-23890
75.
Josefsen, K.,
Sorensen, L. R.,
Buschard, K.,
and Birkenbach, M.
(1999)
Diabetologia
42,
195-203
76.
Ayala, J. E.,
Streeper, R. S.,
Desgrosellier, J. S.,
Durham, S. K.,
Suwanichkul, A.,
Svitek, C. A.,
Goldman, J. K.,
Barr, F. G.,
Powell, D. R.,
and O'Brien, R. M.
(1999)
Diabetes
48,
1885-1889
77.
Guo, S.,
Rena, G.,
Cichy, S.,
He, X.,
Cohen, P.,
and Unterman, T.
(1999)
J. Biol. Chem.
274,
17184-17192
78.
Tang, E. D.,
Nunez, G.,
Barr, F. G.,
and Guan, K. L.
(1999)
J. Biol. Chem.
274,
16741-16746
79.
Shepherd, P. R.,
Withers, D. J.,
and Siddle, K.
(1998)
Biochem. J.
333,
471-490
80.
Fleischmann, M.,
and Iynedjian, P. B.
(2000)
Biochem. J.
349,
13-17
81.
Osborne, T. F.
(2000)
J. Biol. Chem.
275,
32379-32382
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
TOP
INTRODUCTION
The Glucose Signaling PathwayThis article has been cited by other articles:
|
|
 |
|
  T. Hartley, J. Brumell, and A. Volchuk Emerging roles for the ubiquitin-proteasome system and autophagy in pancreatic {beta}-cells Am J Physiol Endocrinol Metab, January 1, 2009; 296(1): E1 - E10. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Perilhou, C. Tourrel-Cuzin, I. Kharroubi, C. Henique, V. Fauveau, T. Kitamura, C. Magnan, C. Postic, C. Prip-Buus, and M. Vasseur-Cognet The Transcription Factor COUP-TFII Is Negatively Regulated by Insulin and Glucose via Foxo1- and ChREBP-Controlled Pathways Mol. Cell. Biol., November 1, 2008; 28(21): 6568 - 6579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Tsatsos, L. B. Augustin, G. W. Anderson, H. C. Towle, and C. N. Mariash Hepatic Expression of the SPOT 14 (S14) Paralog S14-Related (Mid1 Interacting Protein) Is Regulated by Dietary Carbohydrate Endocrinology, October 1, 2008; 149(10): 5155 - 5161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. N. Davies, B. L. O'Callaghan, and H. C. Towle Glucose Activates ChREBP by Increasing Its Rate of Nuclear Entry and Relieving Repression of Its Transcriptional Activity J. Biol. Chem., August 29, 2008; 283(35): 24029 - 24038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Santt, T. Pfirrmann, B. Braun, J. Juretschke, P. Kimmig, H. Scheel, K. Hofmann, M. Thumm, and D. H. Wolf The Yeast GID Complex, a Novel Ubiquitin Ligase (E3) Involved in the Regulation of Carbohydrate Metabolism Mol. Biol. Cell, August 1, 2008; 19(8): 3323 - 3333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jansen, M. Pantaleon, and P. L Kaye Characterization and Regulation of Monocarboxylate Cotransporters Slc16a7 and Slc16a3 in Preimplantation Mouse Embryos Biol Reprod, July 1, 2008; 79(1): 84 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Humphrey and S. G. Rudrappa Increased Glucose Availability Activates Chicken Thymocyte Metabolism and Survival J. Nutr., June 1, 2008; 138(6): 1153 - 1157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jason Collier, P. Zhang, K. B. Pedersen, S. J. Burke, J. W. Haycock, and D. K. Scott c-Myc and ChREBP regulate glucose-mediated expression of the L-type pyruvate kinase gene in INS-1-derived 832/13 cells Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E48 - E56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Guillemain, G. Filhoulaud, G. Da Silva-Xavier, G. A. Rutter, and R. Scharfmann Glucose Is Necessary for Embryonic Pancreatic Endocrine Cell Differentiation J. Biol. Chem., May 18, 2007; 282(20): 15228 - 15237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M J Moreno-Aliaga, M M Swarbrick, S Lorente-Cebrian, K L Stanhope, P J Havel, and J A Martinez Sp1-mediated transcription is involved in the induction of leptin by insulin-stimulated glucose metabolism J. Mol. Endocrinol., May 1, 2007; 38(5): 537 - 546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Ma, Y. Y. Sham, K. J. Walters, and H. C. Towle A critical role for the loop region of the basic helix-loop-helix/leucine zipper protein Mlx in DNA binding and glucose-regulated transcription Nucleic Acids Res., January 12, 2007; 35(1): 35 - 44. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Choi, M. Lee, A. L. Shiu, S. J. Yo, and G. W. Aponte Identification of a protein hydrolysate responsive G protein-coupled receptor in enterocytes Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G98 - G112 |