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)

Studies of adipocyte metabolism were performed in twelve male subjects with normal plasma lipids and eleven male patients with Type IV or Type V hyperlipoproteinemia. Patients with obesity or diabetes mellitus were excluded from the study. Although all patients had normal glucose tolerance tests, the blood glucose levels during these tests were higher in the hyperlipoproteinemic patients than in the normal control subjects and the plasma insulin responses were even more strikingly elevated in the hyperlipemic group. Adipocytes isolated from hypertriglyceridemic subjects were larger than those obtained from normal individuals and exhibited increased activities of both Type I and Type II hexokinase and increased rates of glucose oxidation and lipogenesis from glucose. Cell size, hexokinase isoenzyme activities and rates of lipogenesis from glucose were all strongly correlated with each other, but none of these measurements were correlated with glucose oxidation. It is not known how the adipocyte abnormalities are related to the lipid transport disorder.
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PMID:Hyperinsulinemia and enlarged adipocytes in patients with endogenous hyperlipoproteinemia without obesity or diabetes mellitus. 112 8

The effects of exercise and of food restriction on Zucker obese and lean rats were studied. Zucker obese rats pair-fed to lean littermates gained more body fat on the same intake indicating greater efficiency of diet utilization. Exercise significantly reduced the fat pad weights and body fat content of obese rats. Serum insulin levels were higher in the obese rats and were not influenced by exercise. Exercise had no effect on adipose cellularity of the obese rats. Liver tissue in vitro lipogenic capacity and lipogenic enzyme activities were significantly elevated in obese rats. Exercise increased liver tissue hexokinase and in vitro lipogenesis in lean rats. Exercise increased pentose phosphate pathway enzymes in adipose tissue from lean rats only. Although exercise reduced fat content significantly, obese rats were still fatter (27.7% fat) than the lean controls (6.4% fat). The protein content of obese rats was significantly increased by exercise, indicating that physical activity is important in the regulation of protein metabolism.
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PMID:Effects of exercise and of food restriction on the development of spontaneous obesity in rats. 112 64

Administration of L-thyroxine into intact rats caused a distinct increase in the activity of hexokinase in liver tissue. In the isoenzyme spectrum of hexokinase the activity of hexokinase II was increased significantly. After repeated administration of insulin, liver tissue cells lost their capacity to respond to the hormone administration by induction of hexokinase. Administration of L-thyroxine into animals caused a distinct increase in the hexokinase activity in liver tissue. In isoenzyme spectrum of hexokinase under effect of L-thyroxine a significant increase in the hexokinase II activity was also observed.
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PMID:[Effect of L-thyroxine on the activity and isoenzymatic spectrum of liver hexokinase in intact and insulin-resistant rats]. 113 5

A study was made of the effect of food with a high glucose content given to albino rats for a long time on blood sugar and insulin. Changes in the activity of hexokinase and pyruvickinase in the liver were also investigated. Food with a high glucose content given to rats for 90--100 days led to an increase in the blood sugar and insulin level. The activity of hexokinase and pyruvickinase rose markedly by the 40th--60th day of feeding, and fell to the initial level by the 80th--90th day. Thus, in case of a prolonged action of insulin on the organism as a result of prolonged stimulation of the insular apparatus of the pancreas by glucose there developed signs of peculiar insulin-resistance.
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PMID:[Effect of prolonged feeding of glucose to rats on the levels of sugar and insulin in the blood and the activity of key glycolysis enzymes in the liver]. 114 26

The influence of orally administered carbohydrates and bicycle work on muscle hexokinase activity, blood glucose, and serum insulin levels were studied in 6 young men. Continuously administered glucose of a total amount of 150 g caused a significant increase in hexokinase activity within 3 hrs. Working at a load of 155 to 195 Watt led to an initial increase of hexokinase activity. At the end of the working period hexokinase activity had fallen to resting values. The possible mechanisms of action are discussed.
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PMID:[The influence of bicycle ergometer work and oral glucose administration on the muscle hexokinase activity in man (author's transl)]. 119 93

Pre-incubation of rat adipose tissue from ad lib fed rats in the presence of 1.2 U/ml insulin and 2.8 x 10(-7) M prostaglandin F2 alpha for 16 hours in a gas atmosphere of 5% O2 led to an increase in glucose-6-phosphate dehydrogenase activity. No increase in glycerol-3-phosphate dehydrogenase or hexokinase activities were noted. Actinomycin D (50 micrograms/ml) and dehydroepiandrosterone (120 micrograms/ml) attenuated this increase and the increase in incorporation of [1-14C] glucose into carbon dioxide and tissue seen under these conditions. No increase in glucose-6-phosphate dehydrogenase was seen when pre-incubation was made in a gas atmosphere containing 20% O2. Although dehydroepiandrosterone inhibited both enzyme activity and isotope incorporation in a 20% O2 gas atmosphere, actinomycin D was without effect.
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PMID:In vitro influence of oxygenation on enzymes of rat adipose tissue. 130 32

The gene encoding human glucokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1), a major component of glucose sensing in pancreatic islet beta-cells, was isolated and characterized. The gene was shown by Southern blotting to exist as a single copy in the genome which mapped to chromosome 7p. It contained 12 exons including two tissue-specific first exons, one active in islet beta-cells (1B), and the other active in liver (1H), and one optional cassette exon which was expressed as a minor form in the liver. Thus the three previously reported isoforms of glucokinase mRNA were the result of tissue-specific activation of separate liver and islet promoters and subsequent alternative splicing events. Eleven exons, including 1H and the optional cassette exon 2A, were scattered over 16 kilobase (kb) in the genome, while exon 1B was separated from the rest by at least 20 kb. Although the islet promoter was found to lack a TATA box, a major transcript from the islet promoter was mapped 486 nucleotides upstream of the translation initiation site. The presence in the islet glucokinase promoter of the potential control element GCCACCAG, a homology of the regulatory element present in both human insulin (GCCACCGG) and rat insulin (GCCATCTG) genes, implied a possible tissue-specific regulatory role of this element. The liver promoter was found to contain a TATA box-like sequence, and transcription was initiated predominantly at 168 nucleotides upstream of the translation initiation site of the major isoform. A new highly polymorphic microsatellite, composed of a compound imperfect dinucleotide repeat [GT]15[GA]8CA[GA]7CA[GA]3AA[GA]2, was mapped 6 kb upstream of islet exon 1. A polymerase chain reaction-based assay was developed, and seven different sized alleles were identified in American Blacks. The sequence information reported here, along with the new polymorphic marker, will make it possible to clarify the molecular basis of potential glucokinase defects in noninsulin-dependent diabetes mellitus patients and may further elucidate the nature of genetic susceptibility to the development of this common metabolic disease.
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PMID:Human glucokinase gene: isolation, structural characterization, and identification of a microsatellite repeat polymorphism. 135 40

1. Time-curves of insulin effects on energy-producing systems in different cellular compartments of rat diaphragm muscle have revealed: (a) a rapid (within minutes) and transient stimulatory effect of insulin on cytoskeletal phosphofructokinase and aldolase and mitochondrial hexokinase. (b) A slower and consistent stimulatory effect on glucose 1,6-bisphosphate level, with concomitant gradual activation of cytosolic phosphofructokinase. Fructose 2,6-bisphosphate levels were not changed by insulin. (c) Lactate concentration correlated with the stimulation of cytoskeletal and cytosolic glycolysis. 2. Calmodulin antagonists, trifluoperazine or CGS 9343B, prevented all these effects of insulin. 3. These results suggest that cytoskeletal glycolysis and mitochondrial oxidation are the source of ATP for the rapid actions of insulin, whereas cytosolic glycolysis is the source of ATP for the slow actions of insulin. Calmodulin is involved in all these effects of insulin.
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PMID:Sequence of insulin effects on cytoskeletal and cytosolic phosphofructokinase, mitochondrial hexokinase, glucose 1,6-bisphosphate and fructose 2,6-bisphosphate levels, and the antagonistic action of calmodulin inhibitors, in diaphragm muscle. 139 93

Voluntary wheel running induces an increase in the concentration of the regulatable glucose transporter (GLUT4) in rat plantaris muscle but not in soleus muscle (K. J. Rodnick, J. O. Holloszy, C. E. Mondon, and D. E. James. Diabetes 39: 1425-1429, 1990). Wheel running also causes hypertrophy of the soleus in rats. This study was undertaken to ascertain whether endurance training that induces enzymatic adaptations but no hypertrophy results in an increase in the concentration of GLUT4 protein in rat soleus (slow-twitch red) muscle and, if it does, to determine whether there is a concomitant increase in maximal glucose transport activity. Female rats were trained by treadmill running at 25 m/min up a 15% grade, 90 min/day, 6 days/wk for 3 wk. This training program induced increases of 52% in citrate synthase activity, 66% in hexokinase activity, and 47% in immunoreactive GLUT4 protein concentration in soleus muscles without causing hypertrophy. Glucose transport activity stimulated maximally with insulin plus contractile activity was increased to roughly the same extent (44%) as GLUT4 protein content in soleus muscle by the treadmill exercise training. In a second set of experiments, we examined whether a swim-training program increases glucose transport activity in the soleus in the presence of a maximally effective concentration of insulin. The swimming program induced a 44% increase in immunoreactive GLUT4 protein concentration. Glucose transport activity maximally stimulated with insulin was 62% greater in soleus muscle of the swimmers than in untrained controls. Training did not alter the basal rate of 2-deoxyglucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose transporters and maximal transport are increased in endurance-trained rat soleus. 139 70

Various strategies to improve the therapeutic index of anticancer agents aim at inducing, by stimulation of aerobic glycolysis, temporary pH differences between malignant and normal tissues which can be exploited to activate cytotoxic agents selectively in tumors. We have investigated whether the pH reduction induced by glucose, the "drug" commonly used to increase lactic acid production in malignant tissues, can be augmented by pharmacological manipulation of tumor cell glycolysis. At normal plasma glucose concentration (6 +/- 1 mM), inorganic phosphate, a modifier of hexokinase and phosphofructokinase activity, had no effect on pH in two transplanted rat tumors and a human tumor xenograft line (average pH, 6.80; range, 6.65-6.95). When plasma glucose concentration was raised to 30 +/- 3 mM by i.v. infusion of glucose, inorganic phosphate reduced the pH in those tumors which exhibited only a moderate pH response to glucose per se (mean pH, 6.60) to an average value of 6.20 (range, 6.05-6.35). In the same setting, insulin, continuously infused at dose rates up to 600 milliunits/kg body weight/min, did not result in acidification of tumor tissue exceeding that induced by glucose alone. However, the H+ ion activity in both transplanted rat tumors and human tumor xenografts was increased by m-iodobenzylguanidine (MIBG), an inhibitor of mitochondrial respiration. For example, at normoglycemia, MIBG reduced the mean pH in a human mesothelioma xenograft from 6.90 to 6.70. This pH value was further reduced to 6.20 by simultaneous low-dose i.v. glucose infusion (plasma glucose concentration, 14 +/- 3 mM). The acidosis induced by inorganic phosphate and MIBG was tumor specific. Normal tissues of tumor-bearing hosts were only marginally sensitive to hyperphosphatemia or MIBG administration. These results indicate that the known stimulatory effect of exogenous glucose on lactic acid production in malignant tumors in vivo can be further accentuated or, as in the case of MIBG, partially replaced by pharmacological manipulation of aerobic glycolysis using clinically established drugs.
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PMID:pH in human tumor xenografts and transplanted rat tumors: effect of insulin, inorganic phosphate, and m-iodobenzylguanidine. 142 63


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