Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.1.1 (hexokinase)
5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sequential changes in the expression of two glucose transporter isoforms (GLUT1, GLUT2), and in the activities of hexokinase, pyruvate kinase and malic enzyme during the development of rat renal basophilic cell tumors were studied using histochemical techniques. Early basophilic cell tubules are similar to proximal convoluted tubules (PCT) in their overall histochemical pattern, particularly in the expression of glucose transporters, suggesting that basophilic cell tubules and tumors derived from them arise from PCT. In comparison with PCT, basophilic cell tubules show slightly increased activities of all the enzymes studied. In basophilic cell tumors, markedly elevated hexokinase and pyruvate kinase activities are accompanied by a considerable reduction in the expression of GLUT2. GLUT1 expression is not found in basophilic cell tubules or PCT. Small basophilic cell tumors also do not express GLUT1, but GLUT1 is regularly expressed in several cell layers surrounding necrotic areas within large basophilic cell tumors. Our results indicate that increased glycolytic activity and reduced GLUT2 expression take place during the development of renal basophilic cell tumors.
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PMID:Expression of glucose transporter isoforms (GLUT1, GLUT2) and activities of hexokinase, pyruvate kinase, and malic enzyme in preneoplastic and neoplastic rat renal basophilic cell lesions. 768 99

Renal oncocytomas, which have previously been shown to originate from the collecting duct system, were induced in male Sprague-Dawley rats by oral administration of N-nitrosomorpholine (NNM) for 7 weeks. The expression of glucose transporter isoforms GLUT1 and GLUT2, and of several enzymes involved in glucose metabolism [hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malate dehydrogenase (MDH)] were studied by cytochemical approaches in serial cryostat sections of the kidney 12, 23 and 34 weeks after withdrawal of NNM. Oncocytic tubules connected with collecting ducts were first observed 23 weeks, and oncocytomas 34 weeks after withdrawal. The cytochemical pattern of oncocytic tubules and oncocytomas was similar, but differed markedly from that of normal collecting ducts in nearly all variables studied; expression of GLUT1 and hexokinase I proteins were strongly increased; activities of HK, PK and MDH were elevated, while LDH activity was reduced. These results suggest that oncocytic transformation is associated with fundamental changes in energy metabolism which differ from those in cell lineages leading to other types of renal cell tumours, such as clear/acidophilic and basophilic cell tumours. The characteristic over-expression of GLUT1 may be used as a diagnostic criterion for the discrimination between oncocytes and acidophilic (granular) cells in clear/acidophilic renal cell tumours which show a reduced expression of this glucose transporter protein.
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PMID:Over-expression of glucose transporter isoform GLUT1 and hexokinase I in rat renal oncocytic tubules and oncocytomas. 792 15

Metabolic control analyses of glucose utilization were performed for four groups of working rat hearts perfused with Krebs-Henseleit buffer containing 10 mM glucose only, or with the addition of 4 mM D-beta-hydroxybutyrate/1 mM acetoacetate, 100 nM insulin (0.05 unit/ml), or both. Net glycogen breakdown occurred in the glucose group only and was converted to net glycogen synthesis in the presence of all additions. The flux of [2-3H]glucose through P-glucoisomerase (EC 5.3.1.9) was reduced with ketones, elevated with insulin, and unchanged with the combination. Net glycolytic flux was reduced in the presence of ketones and the combination. The flux control coefficients were determined for the portion of the pathway involving glucose transport to the branches of glycogen synthesis and glycolysis. Major control was divided between the glucose transporter and hexokinase (EC 2.7.1.1) in the glucose group. The distribution of the control was slightly shifted to hexokinase with ketones, and control at the glucose transport step was abolished in the presence of insulin. Analysis of the pathway from 3-P-glycerate to pyruvate determined that the major control was shared by enolase (EC 4.2.1.1) and pyruvate kinase (EC 2.7.1.40) in the glucose group. Addition of ketones, insulin, or the combination shifted the control to P-glycerate mutase (EC 5.4.2.1) and pyruvate kinase. These results illustrate that the control of the metabolic flux in glucose metabolism of rat heart is not exerted by a single enzyme but variably distributed among enzymes depending upon substrate availability, hormonal stimulation, or other changes of conditions.
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PMID:Control of glucose utilization in working perfused rat heart. 792 51

A Xenopus oocyte expression system was used to examine how glucose transporters (GLUT 2 and GLUT 3) and glucokinase (GK) activity affect glucose utilization. Uninjected oocytes and low rates of both glucose transport and phosphorylation; expression of GLUT 2 or GLUT 3 increased glucose phosphorylation approximately 20-fold by a low Km, endogenous hexokinase at glucose concentrations < or = 1 mM, but not at higher glucose concentrations. Coexpression of functional GK isoforms with GLUT 2 or 3 increased glucose utilization approximately an additional two- to threefold primarily at the physiologic glucose concentrations of 5-20 mM. The Km for glucose of both the hepatic and beta cell isoforms of GK, determined in situ, was approximately 5-10 mM when coexpressed with either GLUT 2 or GLUT 3. The increase in glucose utilization by coexpression of GLUT 3 and GK was dependent upon glucose phosphorylation since two missense GK mutations linked with maturity-onset diabetes, 182: Val-->Met and 228:Thr-->Met, did not increase glucose utilization despite accumulation of both a similar amount of immunoreactive GK protein and glucose inside the cell. Coexpression of a mutant GK and a normal GK isoform did not interfere with the function of the normal GK enzyme. Since the coexpression of GK and a glucose transporter in oocytes resembles conditions in the hepatocyte and pancreatic beta cell, these results indicate that increases in glucose utilization at glucose concentrations > 1 mM depend upon both a functional glucose transporter and GK.
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PMID:Coexpression of glucose transporters and glucokinase in Xenopus oocytes indicates that both glucose transport and phosphorylation determine glucose utilization. 792 12

A number of pancreatic beta-tumor cell (beta TC) lines have been derived from insulinomas arising in transgenic mice expressing the SV40 T antigen gene under control of the insulin promoter. Some of these lines secrete insulin in response to physiological glucose concentrations. However, this phenotype is unstable. After propagation in culture, these nonclonal lines become responsive to subphysiological glucose levels and/or manifest reduced insulin release. Here we report the use of soft-agar cloning to isolate single-cell clones from a beta TC line, which give rise to sublines that maintain correct glucose responsiveness and high insulin production and secretion for > 55 passages (over a year) in culture. One of these clonal lines, denoted beta TC6-F7, was characterized in detail. beta TC6-F7 cells expressed high glucokinase and low hexokinase activity, similarly to normal islets. In addition, they expressed mRNA for the GLUT2 glucose transporter isotype and no detectable GLUT1 mRNA, as is characteristic of normal beta-cells. These results demonstrate that transformed beta-cells can maintain a highly differentiated phenotype during prolonged propagation in culture, which has implications for the development of continuous beta-cell lines for transplantation therapy of diabetes.
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PMID:Clonal insulinoma cell line that stably maintains correct glucose responsiveness. 795 92

Uptake and metabolism of mannose were studied in astroglia-rich primary cultures derived from neonatal rat brains. A saturable component of mannose uptake was found with half-maximal uptake at 6.7 +/- 1.0 mM mannose. In addition, a non-saturable component dominated the uptake at high concentrations of mannose. Glucose, cytochalasin B, or phloretin in the incubation buffer inhibited the carrier-mediated uptake of mannose. Within the astroglial cells mannose is phosphorylated to mannose-6-phosphate. In cell homogenates, the KM value of mannose-phosphorylating activity was determined to be 24 +/- 7 microM. The Vmax value of this activity is only 40% that of glucose-phosphorylating activity. Mannose-6-phosphate was converted to fructose-6-phosphate by mannose-6-phosphate isomerase. The specific activity of this enzyme in homogenates of astroglial cultures was higher than that of hexokinase. Two products of mannose utilization in astroglial cells are glycogen and lactate. The amounts of each of these products increased with increasing concentrations of mannose. In contrast to the generation of lactate, that of glycogen from mannose was enhanced in the presence of insulin. In conclusion, we suggest that mannose is taken up into the cells of astroglia-rich primary cultures by the glial glucose transporter and is metabolized to fructose-6-phosphate within the astroglial cells.
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PMID:Utilization of mannose by astroglial cells. 813 58

Superovulated mouse oocytes and embryos were isolated and incubated with nontracer concentrations of 2-deoxyglucose, an analog of glucose, which is transported into the cells by glucose transporter and phosphorylated by hexokinase to 2-deoxyglucose 6-phosphate; it is not rapidly metabolized further, and accumulates in the cytosol. Using our non-radiometric and enzymatic microassay method, we determined 2-deoxyglucose and 2-deoxyglucose 6-phosphate amounts in individual oocytes and preimplantation embryos after the incubation. Hexokinase activity increased continuously and exponentially during development from follicular oocytes to blastocysts. Endogenous glucose and glucose 6-phosphate decreased precipitously from follicular oocytes to unfertilized and ovulated oocytes. Fertilization induced rapid increases in glucose and glucose 6-phosphate concentrations, which increased exponentially thereafter during embryonic development. 2-Deoxyglucose incorporation and 2-deoxyglucose 6-phosphate formation were undetectable in unfertilized oocytes. However, when cumulus-oocyte complexes were incubated with 2-deoxyglucose, 2-deoxyglucose was incorporated into cumulus cells surrounding follicular oocytes and transported via the gap junctions into the follicular oocytes. Fertilization triggered facilitative 2-deoxyglucose transport in one-cell embryos, and the capacities of 2-deoxyglucose incorporation and 2-deoxyglucose 6-phosphate formation developed along with the maturation of preimplantation embryos.
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PMID:Development of glucose utilization studied in single oocytes and preimplantation embryos from mice. 814 45

Glucose transport and phosphorylation are the first steps in the utilization of extracellular glucose by skeletal muscle. We have examined the relationships between proteins mediating these steps in single fibers of identified type dissected from rabbit skeletal muscle. The level of the glucose transporter isoform GLUT4, measured by immunoblotting, varied among fibers by a factor of 20 (slow oxidative > fast oxidative glycolytic > fast glycolytic). In fibers from the tibialis anterior muscle, GLUT4 was correlated (r2 = 0.75) with the activity of malate dehydrogenase, an enzyme representative of oxidative energy metabolism. In these fibers a strong correlation (r2 = 0.70) was also observed between GLUT4 and hexokinase activity. GLUT1 levels were barely detectable, regardless of fiber type. To investigate the possible role of muscle activity in controlling the expression of transporters, tibialis anterior muscles were activated by chronic electrical stimulation of the peroneal nerves. GLUT1 levels increased after 1 day of stimulation to a plateau that was severalfold higher than the level in non-stimulated cells. Hexokinase activity and the GLUT4 level changed in parallel: both were increased by approximately 2.5-fold after 1 day and by 14-fold after 21 days. Thus, while both GLUT1 and GLUT4 were regulated by muscle activity, only GLUT4 expression was coordinated with the expression of hexokinase.
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PMID:Glucose transporters in single skeletal muscle fibers. Relationship to hexokinase and regulation by contractile activity. 817 14

GLUT4 glucose transporter content and glucose transport capacity are closely correlated in skeletal muscle. In this study, we tested the hypothesis that a rapid increase in GLUT4 expression occurs as part of the early adaptive response of muscle to exercise and serves to enhance glycogen storage. Rats exercised by swimming had a approximately 2-fold increase in GLUT4 mRNA and a 50% increase in GLUT4 protein expression in epitrochlearis muscle 16 h after one prolonged exercise session. After a 2nd day of exercise, muscle GLUT4 protein was increased further to approximately 2-fold while there was no additional increase in GLUT4 mRNA. Muscle hexokinase activity also doubled in response to 2 days of exercise. Glucose transport activity maximally stimulated with insulin, contractions, or hypoxia was increased roughly in proportion to the adaptive increase in GLUT4 protein in epitrochlearis muscles. Treatment with insulin prior to subcellular fractionation of muscle resulted in a approximately 2-fold greater increase in GLUT4 content of a plasma membrane fraction in the 2-day swimmers than in controls. When epitrochlearis muscles were incubated with glucose and insulin, glycogen accumulation over 3 h was twice as great in muscles from 2-day swimmers as in control muscles. Our results show that a rapid increase in GLUT4 expression is an early adaptive response of muscle to exercise. This adaptation appears to be mediated by pretranslational mechanisms. We hypothesize that the physiological role of this adaptation is to enhance replenishment of muscle glycogen stores.
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PMID:Exercise induces rapid increases in GLUT4 expression, glucose transport capacity, and insulin-stimulated glycogen storage in muscle. 818 45

The insulin-secretory response to glucose is defective in the RINm5F insulin-producing tumour cell line. Stable transfection with human low-affinity GLUT2 glucose-transporter cDNA revealed a significant improvement in stimulus-secretion coupling in these insulinoma cells. 3-O-Methylglucose uptake increased 10-fold in the concentration range 10-20 mM, whereas non-transfected control cells were unresponsive. Northern-blot analysis revealed a 7-fold increase in expression of the insulin gene in the GLUT2-transfected RINm5F cell clone T1. In contrast, glucokinase and GLUT1 glucose-transporter mRNA gene expression were not affected by transfection with GLUT2 glucose-transporter cDNA. The insulin content of transfected RINm5F cells was 7-fold higher after tissue culture at high glucose concentrations than in non-transfected controls. GLUT2-transfected RINm5F cells also regained insulin-secretory responsiveness toward high glucose concentrations. Tissue culture for 72 h in 20 mM glucose induced glucokinase activity in the GLUT2-transfected RINm5F clone T1, raising the glucokinase/hexokinase phosphorylation ratio from 0.2 to 0.6. The experiments demonstrate that an increased glucose uptake via a low-affinity glucose transporter and an increased metabolic flux rate are important factors in the induction of insulin-gene expression and glucokinase activity and thus improved glucose-induced biosynthesis and secretion of insulin in RINm5F insulinoma cells.
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PMID:Insulin secretion, insulin content and glucose phosphorylation in RINm5F insulinoma cells after transfection with human GLUT2 glucose-transporter cDNA. 825 Aug 30


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