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GCK — INS
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Cabrera-Valladares et al., Endocrinology 1999
:
Because
glucokinase activity
controls insulin secretion, we also investigated the effect of retinoic acid on insulin secretion
Romero-Navarro et al., Endocrinology 1999
:
Because
glucokinase activity
controls insulin secretion, we also investigated the effect of biotin on insulin release
Lynch et al., Diabetes 2000
:
In pancreatic beta-cells,
glucokinase (GK) , the rate limiting enzyme in glycolysis,
mediates glucose induced
insulin release by regulating intracellular ATP production
Iynedjian et al., Biochem J 2000
:
Together with the inhibition by phosphoinositide 3-kinase inhibitors, they suggest that the activation of PKB might be critical in mediating the
induction of
glucokinase by
insulin
Baltrusch et al., J Biol Chem 2001
:
Changes in fructose-2,6-bisphosphate levels and modulation of PFK-2/FBPase-2 activities may participate in the physiological regulation of
glucokinase mediated glucose induced
insulin secretion
O'Driscoll et al., In Vitro Cell Dev Biol Anim 2002
:
Coexpression of GLUT2 and
GCK did not
result in glucose stimulated
insulin secretion
Rizzo et al., J Biol Chem 2002
:
Glucokinase (GK) activity is
essential for the physiological regulation of
insulin secretion by glucose
Ribaux et al., Endocrinology 2002
:
Additionally, the current results show that signal transducer and activator of transcription 5 activation is neither necessary nor sufficient for the
insulin dependent induction of hepatic
glucokinase
Nouspikel et al., Eur J Biochem 1992
:
Insulin signalling and
regulation of
glucokinase gene expression in cultured hepatocytes ... Three inhibitors of this class of enzymes were tested for their effect on the
insulin dependent
induction of the
glucokinase gene in hepatocytes ... A specific inhibitor of protein phosphatases PP1 and PP2A, okadaic acid, was shown to abolish the transcriptional
response of the
glucokinase gene to
insulin
Ribaux et al., Biochem J 2003
:
Analysis of the role of protein kinase B ( cAKT ) in
insulin dependent induction of
glucokinase and sterol regulatory element binding protein 1 ( SREBP1 ) mRNAs in hepatocytes ... This resulted in the inhibition of
insulin dependent increases in
GCK and SREBP1 mRNAs ... The stimulation of gene expression by constitutively active PKB-CaaX and inhibition of the insulin effect by ceramide are compatible with a role for PKB in the
insulin dependent induction of
GCK and SREBP1
Nouspikel et al., FEBS Lett 1992
:
Unimpaired
effect of
insulin on
glucokinase gene expression in hepatocytes challenged with amylin
Dich et al., Anal Biochem 1992
:
The dose-response relationship for
induction by
insulin of
glucokinase and pyruvate kinase was shifted to the left by a factor of 9 and 5, respectively, as compared to conventional, stationary cultures
Roth et al., J Biol Chem 2004
:
The transcription factors HIF-1 and HNF-4 and the coactivator p300 are involved in
insulin regulated
glucokinase gene expression via the phosphatidylinositol 3-kinase/protein kinase B pathway ... In primary rat hepatocytes, pO ( 2 ) modulated
insulin dependent
glucokinase (GK) gene expression was abolished by wortmannin an inhibitor of phosphatidylinositol 3-kinase (PI3K)
Kim et al., J Biol Chem 2004
:
SREBP-1c mediates the
insulin dependent hepatic
glucokinase expression
Marotta et al., Arch Biochem Biophys 2005
:
The central
role of human pancreatic
glucokinase in
insulin secretion and, consequently, in maintenance of blood glucose levels has prompted investigation into identification of ATP binding site residues and examination of ATP- and glucose binding interactions
Galán et al., Biochem J 2006
(Diabetes Mellitus, Type 2...) :
Glucokinase acts as the pancreatic glucose sensor and
plays a critical role in the regulation of
insulin secretion by the beta-cell
Gregori et al., FEBS Lett 2006
:
Insulin regulation of
glucokinase gene expression : evidence against a role for sterol regulatory element binding protein 1 in primary hepatocytes ... The sterol regulatory-element binding protein-1c ( SREBP-1c ) has emerged as a mediator of
insulin effects on gene transcription, particularly on
glucokinase (GK)
Zhang et al., Biochem J 2006
:
The inhibitory effect of resveratrol on insulin signalling is also demonstrated at mRNA level, where resveratrol reverses
insulin effects on phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, fatty acid synthase and
glucokinase
Hansmannel et al., Biochem J 2006
:
Insulin induction of
glucokinase and fatty acid synthase in hepatocytes : analysis of the roles of sterol-regulatory-element binding protein-1c and liver X receptor
Baltrusch et al., Endocrinology 2006
:
The glucose sensor enzyme
glucokinase plays a pivotal role in the regulation of glucose induced
insulin secretion in pancreatic beta-cells
Tiedge et al., Dtsch Med Wochenschr 2006
(Diabetes Mellitus, Type 2) :
In this way
glucokinase activators increase glucose
induced insulin secretion and inhibit hepatic glucogenesis
García-Herrero et al., Diabetologia 2007
(Diabetes Mellitus, Type 2) :
Glucokinase (GCK) acts as a glucose sensor in the pancreatic beta cell and
regulates insulin secretion
Terauchi et al., J Clin Invest 2007
(Hyperplasia...) :
Glucokinase (Gck) functions as a glucose sensor for insulin secretion, and in mice fed standard chow, haploinsufficiency of beta cell-specific Gck ( Gck ( +/- ) )
causes impaired
insulin secretion to glucose, although the animals have a normal beta cell mass
Uhles et al., FASEB J 2007
:
We now demonstrate that
insulin stimulated transcription of c-fos and
glucokinase genes is activated simultaneously in the insulin producing beta-cell via IR-B localized in different cellular compartments
Yoshida et al., Endocrinology 2007
:
Glucokinase (GK) plays a key role in the regulation of glucose use and glucose
stimulated insulin secretion in pancreatic islet cells
Egea et al., J Mol Endocrinol 2007
:
We propose a new mechanism that involves Sp1 and Sp3 to mediate
insulin activation of
GCK transcription
Sanz et al., J Endocrinol 2007
:
Effects of glucose and
insulin on
glucokinase activity in rat hypothalamus
Bjørkhaug et al., J Biol Chem 2007
:
Both ubiquitination of hGK and its activation by polyubiquitin chains potentially represent physiological regulatory mechanisms for
glucokinase dependent
insulin secretion in pancreatic beta-cells
Egea et al., Gen Comp Endocrinol 2008
:
Role of Sp1 and SREBP-1a in the
insulin mediated regulation of
glucokinase transcription in the liver of gilthead sea bream ( Sparus aurata ) ... To study the molecular mechanism underlying the regulation of hepatic GCK expression in the carnivorous fish gilthead sea bream ( Sparus aurata ), we analysed the role of sterol regulatory element binding protein-1a ( SREBP-1a ) and specificity protein (Sp) 1 in
insulin dependent
GCK transcription ... Since SREBP-1a and Sp1 may mediate
insulin action on S. aurata
GCK transcription, we analysed the effect of insulin on HepG2 cells transfected with GCK promoter reporter constructs carrying intact or mutated SRE or Sp boxes ... Our findings indicate that Sp1, rather than SREBP-1a, mediates the
insulin dependent induction of S. aurata
GCK
El-Refai et al., Am J Physiol 1976
:
The model predicts that, although insulin can inhibit glucose production by lowering phosphorylase and gluconeogenesis, only an
insulin mediated induction of
glucokinase can account for insulin 's action to potentiate the effect of glucose alone on glycogen synthesis
Pal et al., Drug Discov Today 2009
(Diabetes Mellitus, Experimental...) :
Activators of
glucokinase increase the sensitivity of the enzyme to glucose, leading to increased
insulin secretion and liver glycogen synthesis and a decrease in liver glucose output
Li et al., Diabetes 2009
:
Glucokinase (GCK) and glucose-6-phosphatase catalytic subunit 2 ( G6PC2 ) regulate the glucose cycling step in pancreatic beta-cells and may
regulate insulin secretion
Barbetti et al., Mol Endocrinol 2009
(Genetic Predisposition to Disease...) :
Glucokinase is
essential for glucose stimulated
insulin release from the pancreatic beta-cell, serving as glucose sensor in humans
Hughes et al., J Biol Chem 1991
:
We conclude that
glucokinase expression in AtT20ins cells may be necessary, but is not
sufficient to confer glucose stimulated
insulin secretion
Zhu et al., Am J Physiol Endocrinol Metab 2010
:
Finally, the knockdown of endogenous ERRalpha with specific siRNA ( siERRalpha ) or pharmacological inhibition of ERRalpha with XCT790 attenuated
insulin induced
glucokinase expression
Al-Sheyab et al., Tsitol Genet 2009
(Diabetes Mellitus, Type 2) :
Glucokinase (GCK) acts as a glucose sensor in the pancreatic beta cell and
regulates insulin secretion
Ohyama et al., Eur J Pharmacol 2010
:
Glucokinase activators
increase insulin release from pancreatic beta-cells and hepatic glucose utilization by modifying the activity of glucokinase, a key enzyme in glucose sensing and glycemic regulation
Uchiyama et al., Metabolism 2011
(Diabetes Mellitus, Experimental...) :
Glucokinase regulates
insulin secretion via phosphorylation of glucose
Magnuson et al., Diabetes 1990
:
Expression of this enzyme is differentially regulated ; hepatic
glucokinase is
stimulated by
insulin and repressed by cAMP, whereas beta-cell glucokinase activity is increased by glucose
Liang et al., J Biol Chem 1990
:
It is concluded that ( a ) glucose is the physiological regulator of glucokinase in the islet of Langerhans and that ( b ) the activity of
glucokinase plays a crucial role in glucose induced
insulin secretion
García-Herrero et al., PloS one 2012
(Diabetes Mellitus, Type 2) :
Glucokinase (GK) acts as a glucose sensor in the pancreatic beta-cell and
regulates insulin secretion
Dhanesha et al., Journal of diabetes 2012
(Body Weight...) :
Glucokinase (GK) , by catalysing the first step in glycolysis,
plays an important role in glucose stimulated
insulin secretion and hepatic glucose metabolism
Fu et al., PloS one 2013
(Diabetes Mellitus, Type 2...) :
Glucokinase (GCK) is the key glucose phosphorylation enzyme which has attracted considerable attention as a candidate gene for type 2 diabetes ( T2D ) based on its enzyme function as the first rate limiting step in the glycolysis pathway and
regulates glucose stimulated
insulin secretion
Magnuson et al., J Biol Chem 1989
(Adenoma, Islet Cell...) :
The use of alternative promoters apparently enables the
glucokinase gene to be
regulated by
insulin in the liver and by glucose in the beta cell, thus possibly constituting an important feedback control loop for maintaining glucose homeostasis
Iynedjian et al., J Biol Chem 1989
:
Transcriptional
induction of
glucokinase gene by
insulin in cultured liver cells and its repression by the glucagon-cAMP system
Lenzen et al., Acta Endocrinol (Copenh) 1987
(Adenoma, Islet Cell...) :
The
role of
glucokinase in the regulation of
insulin secretion was examined in normal rat pancreatic islets and in chemically- and radiation induced rat pancreatic B-cell tumours which show an impaired insulin secretory response to glucose ... This observation is consistent with the
induction of
glucokinase by
insulin
Subasinghe et al., Biochem Med 1985
(Diabetes Mellitus, Experimental) :
The insulin-mimetic action of Mn2+ :
involvement of cyclic nucleotides and
insulin in the regulation of hepatic hexokinase and
glucokinase
Kobayashi et al., Acta Med Okayama 1988
:
Insulin increased the activities of
glucokinase ( EC 2.7.1.1 ), phosphofructokinase ( EC 2.7.1.11 ), pyruvate kinase ( EC 2.7.1.40 ) type L and glucose 6-phosphate dehydrogenase ( EC 1.1.1.49 )
Iynedjian et al., J Biol Chem 1988
(Diabetes Mellitus, Experimental) :
Stimulation by
insulin of
glucokinase gene transcription in liver of diabetic rats
Lenzen et al., Acta Endocrinol (Copenh) 1987
:
Thus, inhibition of pancreatic B-cell
glucokinase may
contribute to the inhibition of glucose induced
insulin secretion by alloxan
Sener et al., J Biol Chem 1985
:
It is concluded that the participation of
glucokinase is not
essential for the anomeric specificity of glycolysis and
insulin release in rat pancreatic islets
Miwa et al., Biochem Int 1985
:
Neither isomer was phosphorylated by liver
glucokinase nor
stimulated insulin release from islets ... These results strongly suggest that the inhibition of glucose stimulated insulin release by pseudo-alpha-DL-glucose is due to the inhibition of islet glucokinase by the glucose analog, providing additional evidence for the essential
role of islet
glucokinase in glucose stimulated
insulin release
Kil'dema et al., Vopr Med Khim 1979
(Liver Neoplasms...) :
Effects of hydrocortisone and
insulin on activities of hexokinase and its isoenzymes and on
glucokinase activity were studied in hepatocarcinogenesis, induced in rats by diethyl nitrosamine ...
Insulin , administered within 2 days, caused no effect on the hexokinase activity but the
glucokinase was
activated by 177 %
Schudt et al., Eur J Biochem 1979
:
Glucokinase levels in hepatocytes derived from fasted rats could be elevated from 7.4 to 16.4 mU/mg protein in the
presence of
insulin and triamcinolone ... In cultures treated for 2 days with triamcinolone,
insulin induced a 80 % increase of
glucokinase even in the absence of glucocorticoids
Spence et al., J Biol Chem 1981
:
Role of
insulin , glucose, and cyclic GMP in the regulation of
glucokinase in cultured hepatocytes ... The addition to the medium of glucose, fructose, pyruvate, or lactate enhanced the
insulin induced increase in
glucokinase , but only fructose, pyruvate, and lactate increased the activity of the enzyme in the absence of insulin ... When the phosphorylation of hexoses was blocked by the addition of N-acetylglucosamine to the culture medium, an intermediate level of
glucokinase activity was observed in
response to
insulin
Sibrowski et al., J Biol Chem 1984
(Diabetes Mellitus, Experimental) :
These data indicate that
insulin regulates hepatic
glucokinase synthesis in vivo by increasing glucokinase mRNA ; its effect is reduced by the absence of glucocorticoids or thyroid hormones and is rapidly antagonized by cyclic AMP
Lavender et al., Diabetologia 1983
(Diabetes Mellitus, Experimental...) :
On the assumption that
insulin plays some role in the synthesis of
glucokinase , the possible association between the plasma insulin concentration and hepatic glucokinase activity in mice in which plasma glucose concentrations are similar is discussed
Nordlie et al., Biochim Biophys Acta 1982
(Diabetes Mellitus, Experimental) :
The need for supplemental mechanisms of glucose utilization by high Km hepatic enzyme ( s ) operative in the virtual absence of
insulin dependent
glucokinase also is indicated by these observations and by kinetic analysis
Singh et al., FEBS Lett 1982
:
It is concluded that a high K0.5 glucose phosphorylating enzyme or enzymes compensatory to
insulin dependent
glucokinase is/are involved in rat liver glucose phosphorylation
Noguchi et al., FEBS Lett 1993
(Diabetes Mellitus, Type 2) :
These results indicate that the
regulation of gene expression of
glucokinase and phosphoenolpyruvate carboxykinase, but not of L-type pyruvate kinase, by
insulin is impaired in the liver of the Wistar fatty rat
Iynedjian et al., J Clin Invest 1995
:
The main results are : ( a ) glucokinase accounts for 95 % of the glucose phosphorylation activity of human hepatocytes, although this fact is masked in assays of total liver tissue ; ( b ) glucokinase activity is set at a lower level in human hepatocytes than in rat hepatocytes, and vice-versa for the gluconeogenic enzyme phosphoenolpyruvate carboxykinase ; and ( c ) as previously shown in rat liver,
glucokinase and phosphoenolpyruvate carboxykinase mRNAs are regulated in a reciprocal fashion in human hepatocytes,
insulin inducing the first enzyme and repressing the latter, whereas glucagon has opposite effects
Tiedge et al., Biochem J 1995
:
The mutual
role of glucose and
insulin in the regulation of
glucokinase and GLUT2 glucose transporter gene expression in pancreatic B-cells and liver has been studied in vivo in the rat ... The results suggest that it is glucose which stimulates glucokinase gene expression in pancreatic B-cells whereas the transcriptional regulation of the
glucokinase gene in liver is
directed by
insulin
Beresford et al., Mol Cell Biochem 1994
:
Cytochalisin D exerts stimulatory and inhibitory effects on
insulin induced
glucokinase mRNA expression in hepatocytes ... Cytochalasin-D significantly potentiates
insulin induced
glucokinase mRNA expression at 100 nM concentration but counteracts glucokinase expression at 2-20 microM
Wajngot et al., Diabetes 1994
:
Glucokinase deficiency thus
affects not only
insulin responses to glucose per se but also glucose potentiation of responses to non-nutrient secretagogues
Tosh et al., Biochim Biophys Acta 1994
:
Insulin induced
glucokinase mRNA expression was higher in hepatocytes from fed than from fasted or refed rats whereas PEPCK mRNA expression was lowest in hepatocytes from fasted refed rats
Beresford et al., Biochem Biophys Res Commun 1994
:
Epidermal growth factor counteracts
insulin induced expression of
glucokinase in hepatocytes ... Hepatic
glucokinase is
induced by
insulin and repressed by glucagon ... EGF suppressed the
insulin induced increase in
glucokinase mRNA levels by 50 % indicating that its effect is at least in part at a pretranslational level
Jahodár et al., Cesk Farm 1993
(Diabetes Mellitus) :
Insulin also
stimulates the synthesis of
glucokinase and moderates the degree of gluconeogenesis
Voss-McCowan et al., J Biol Chem 1994
:
Glucokinase regulates
insulin secretion by controlling the rate of glucose phosphorylation
Vaulont et al., FASEB J 1994
:
Whereas the transcription of the
glucokinase gene, for example, is
stimulated by
insulin without the aid of glucose, the transcriptional activation of most glycolytic and lipogenic genes in hepatocytes requires the presence of both glucose and insulin
Lefrançois-Martinez et al., FASEB J 1994
(Liver Neoplasms, Experimental) :
In mhAT3F cells, the insensitivity to insulin might be due to the replacement of
insulin dependent
glucokinase by insulin independent hexokinases able to phosphorylate glucose in the absence of the hormone
Bossard et al., Eur J Biochem 1993
:
The appearance of
glucokinase is principally
due to the increase of plasma
insulin and to the decrease of plasma glucagon concentrations ... It is suggested that the hormonal environment did not allow glucokinase gene expression to be induced in fetal liver and that the absence of expression of
glucokinase in suckling rat liver is
due to the presence of low plasma
insulin and high plasma glucagon levels ... This suggests that these sites could be implicated in the
regulation of
glucokinase gene expression by
insulin and glucagon
Becker et al., J Biol Chem 1996
:
Furthermore,
glucokinase overexpression
enhanced insulin secretion in response to stimulatory glucose or glucose plus arginine by only 36-53 % relative to control islets
Parsa et al., Eur J Biochem 1996
:
Induction of the
glucokinase gene by
insulin in cultured neonatal rat hepatocytes ... Finally, an increase of the sensitivity of hypersensitive site-1 and hypersensitive site-2 to DNase I correlates with the ability of
insulin to
induce glucokinase gene expression in cultured hepatocytes from 1-day-old rats, as observed in previous in vivo studies ... This suggests that neither a prior exposure to insulin nor a simple aging of the fetal cells in the presence of the hormone in culture are instrumental for the full DNase-I hypersensitivity of the two proximal sites necessary for the neonatal
response of the
glucokinase gene to
insulin
Noma et al., Endocrinology 1996
(Acute Disease...) :
Glucokinase (GK) plays a key role in the regulation of glucose induced
insulin secretion, and questions have been raised about its relationship to the glucose transporter GLUT2 and its function in diabetes
Sweet et al., Am J Physiol 1996
:
Effect of a
glucokinase inhibitor on energy production and
insulin release in pancreatic islets
Watada et al., Diabetes 1996
:
The glycolytic enzyme
glucokinase plays a primary role in the glucose-responsive secretion of
insulin , and defects of this enzyme can cause NIDDM
Kietzmann et al., Biochem J 1997
:
Arterial oxygen partial pressures reduce the
insulin dependent induction of the perivenously located
glucokinase in rat hepatocyte cultures : mimicry of arterial oxygen pressures by H2O2
Jungermann et al., Kidney Int 1997
:
Conversely, the
insulin dependent activation of the
glucokinase gene was negatively modulated by oxygen
Kahn et al., Biochimie 1997
:
At the hepatic level, the role of
insulin is mainly to
stimulate the synthesis of
glucokinase , needed for phosphorylation of glucose to glucose 6-phosphate
Cuif et al., FEBS Lett 1997
:
We previously demonstrated that, in hepatocytes in primary culture, the role of
insulin on induction of L-type pyruvate kinase ( L-PK ) gene expression was mainly to
induce glucokinase synthesis, needed for glucose phosphorylation to glucose 6-phosphate
Kietzmann et al., Biochem J 1998
:
Involvement of a local fenton reaction in the reciprocal modulation by O2 of the glucagon dependent activation of the phosphoenolpyruvate carboxykinase gene and the
insulin dependent
activation of the
glucokinase gene in rat hepatocytes ... H2O2 mimicked the action of periportal pO2 in the modulation by O2 of the glucagon dependent activation of the phosphoenolpyruvate carboxykinase ( PCK ) gene and the
insulin dependent
activation of the
glucokinase (GK) gene
Motoyoshi et al., Diabetologia 1998
(Adenoma...) :
Our results suggest that both GLUT2 and
glucokinase are necessary for the glucose stimulated insulin secretion in at least rodent cell lines, and that other element ( s ) are
necessary for a biphasic
insulin secretion typically observed in beta cells
Kahn et al., C R Seances Soc Biol Fil 1998
:
Phosphorylation of glucose to G-6P assured either by
insulin dependent
glucokinase or by another hexokinase isoform