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)

The influence of clofibrate on the glycolytic pathway in liver was studied. The changes in the activity of glucokinase and hexokinase were not significant. A reduction of phosphofructokinase (p less than 0.05) and pyruvate kinase activity was found (p less than 0.0005) during clofibrate feeding. An in vitro inhibition of these enzymes could not be demonstrated by clofibrate up to a concentration of 2.5 mM. Crossover plots of glycolytic intermediates indicate that the reduced pyruvate kinase activity may influence the glycolytic pathway in vivo. Clofibrate feeding induces a lower ATP:ADP ratio, a lower adenylate energy charge and elevates AMP levels in rat liver. This may possibly stimulate the hepatic glycogenolysis and the glucose utilisation by this organ.
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PMID:Alterations of the glycolytic pathway and adenine nucleotide state in livers of clofibrate treated rats. 14 Aug 42

The high-Km glucose transporter, GLUT-2, and the high-Km hexokinase of beta cells, glucokinase (GK), are required for glucose-stimulated insulin secretion (GSIS). GLUT-2 expression in beta cells of Zucker diabetic fatty (ZDF) rats is profoundly reduced at the onset of beta-cell dysfunction of diabetes. Because ZDF rats are homozygous for a mutation in their leptin receptor (OB-R) gene and are therefore leptin-insensitive, we expressed the wild-type OB-R gene in diabetic islets by infusing a recombinant adenovirus (AdCMV-OB-Rb) to determine whether this reversed the abnormalities. Leptin induced a rise in phosphorylated STAT3, indicating that the transferred wild-type OB-R was functional. GLUT-2 protein rose 17-fold in AdCMV-OB-Rb-treated ZDF islets without leptin, and leptin caused no further rise. GK protein rose 7-fold without and 12-fold with leptin. Preproinsulin mRNA increased 64% without leptin and rose no further with leptin, but leptin was required to restore GSIS. Clofibrate and 9-cis-retinoic acid, the partner ligands for binding to peroxisome proliferator-activator receptor alpha (PPARalpha) and retinoid X receptor, up-regulated GLUT-2 expression in islets of normal rats, but not in ZDF rats, in which PPARalpha is very low. Because the fat content of islets of diabetic ZDF rats remains high unless they are treated with leptin, it appears that restoration of GSIS requires normalization of intracellular nutrient homeostasis, whereas up-regulation of GLUT-2 and GK is leptin-independent, requiring only high expression of OB-Rb.
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PMID:Overexpression of leptin receptors in pancreatic islets of Zucker diabetic fatty rats restores GLUT-2, glucokinase, and glucose-stimulated insulin secretion. 975 66