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)

Diabetic states are characterized by a raised serum/islet level of triglycerides and a lowered EC50 (concentration at half-maximal stimulation) for glucose-induced insulin secretion. Culturing islets with long-chain fatty acids (FAs) replicates the basal insulin hypersecretion. In a previous study, we showed that the mechanism involved deinhibition of hexokinase by a 60% decrease in glucose-6-phosphate (G-6-P). The key event was proposed to be an increased phosphofructokinase (PFK) Vmax secondary to an upregulatory effect of the FA metabolite, long-chain acyl-coenzyme A (LC-CoA). We now show another contributory factor, a lowered content of the PFK inhibitor citrate. Citrate synthase Vmax and citrate levels were lowered 45% in rat islets cultured with 250 micromol/l oleate for 24 h. Both effects were reversed by triacsin C, an inhibitor of fatty acyl-CoA synthetase, the enzyme that generates LC-CoA. Culturing islets with high doses of glucose (16.7 mmol/l) for 48 h should also raise cytosolic LC-CoA. As predicted, citrate synthase Vmax was lowered and PFK Vmax was increased, both in a triacsin C-reversible fashion. These results show shared selected functional and biochemical properties in beta-cells of so-called glucotoxicity and lipotoxicity.
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PMID:Shared biochemical properties of glucotoxicity and lipotoxicity in islets decrease citrate synthase activity and increase phosphofructokinase activity. 983 20

Clenbuterol, a beta2-adrenergic-receptor agonist, is known to provoke muscle hypertrophy and a slow-to-fast phenotype change. A more glycolytic phenotype should be paralleled by changes in muscle glycolytic metabolism. Two groups (n=16 for each) of 3-month-old male Wistar rats (UCL: untrained clenbuterol, and ECL: exercised clenbuterol) received a chronic administration of clenbuterol (2 mg/kg body weight/day). Two other groups of animals (U: untrained and E: exercised), were given a 0.9% NaCl solution instead of clenbuterol. E and ECL animals followed an 8-week progressive isometric force strength-training program. Both clenbuterol administration and training resulted in an increase in extensor digitorum longus (EDL) mass despite the fact that this muscle was indirectly mobilised during isometric force strength training. Clenbuterol and training induced a consistent slow-to-fast phenotype change without drastically increasing specific activities of glycolytic enzymes. Except for GAPDH and hexokinase, modifications in glycolytic-enzyme-specific activities were not explained by transcriptional changes. Lactate dehydrogenase activity was not affected by clenbuterol but was strongly augmented by training. In EDL of ECL rats, both treatments presented an opposite effect compensating each other. GLUT1 mRNA expression was augmented in EDL of UCL and ECL animals, whereas monocarboxylate transporter 1 mRNA amounts were decreased in EDL of UCL rats. Citrate synthase activity was reduced by clenbuterol treatment but remained unchanged in EDL of E animals. Creatine kinase activity was enhanced only by clenbuterol alone. These data show that clenbuterol-induced muscle hypertrophy and slow-to-fast phenotype changes are not associated with a glycolytic-enzyme-activity increase. They also suggest that in EDL isometric force strength training can reverse clenbuterol-induced molecular adaptations.
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PMID:Molecular impact of clenbuterol and isometric strength training on rat EDL muscles. 1709 70


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