Gene interactions and pathways from curated databases and text-mining

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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