Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The importance of the glucose transporter isoform, GLUT2, in the construction of glucose-sensitive surrogate insulin-secreting cells was evaluated using murine pituitary AtT20 cells. The cells were double transfected with cDNAs for human preproinsulin (hppI-1) driven by the cytomegalovirus promoter, and human GLUT2 driven by the beta-actin promoter. The stably transfected clone, AtTinsGLUT2.36, which strongly expressed both the hppI-1 and GLUT2 genes, constitutively released 7.5 ng/10(6) cells/24 h of immunoreactive insulin-like material, 75% of which was fully processed mature human insulin. Increasing glucose concentrations in the subphysiological range up to 50 microM increased insulin release, but greater glucose concentrations did not further increase insulin release. Suppression of the low-K(m) glucose-phosphorylating enzyme, hexokinase, with 2-deoxy-D-glucose increased glucose-stimulated insulin release by two- to threefold in the presence of subphysiological and physiological glucose concentrations up to 10 mM. Physiological glucose concentrations increased the amount of GLUT2 mRNA, indicating that the beta-actin promoter responds in a glucose-dependent manner. Implantation of 2 x 10(7) AtTinsGLUT2.36 cells intraperitoneally into streptozotocin-diabetic nude mice slowed the progression of hyperglycaemia. The implanted cells formed vascularised tumour-like cell aggregates attached to the peritoneum. The results demonstrate that the beta-actin promoter is partially regulated by glucose. Expression of GLUT2 enables glucose to enter the cell at high K(m), but high-K(m) glucose phosphorylation is also required to signal glucose-stimulated genes affecting insulin release.
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PMID:Expression of GLUT2 in insulin-secreting AtT20 pituitary cells. 951 84

: Sugars are utilized poorly in fish mainly because of low rates of transport across plasma membrane and phosphorylation. To evaluate whether it is possible to augment carbohydrate metabolism in fish using heterologous genes, expression of human glucose transporter type 1 (hGLUT1) and rat hexokinase type II (rHKII) complementary DNAs cloned with cytomegalovirus promoter was followed in rainbow trout embryos. Both genes were transcribed. Hexokinase activity, undetectable in control, was found in transformed blastulas. Increased rates of 14C-methylglucose uptake and sensitivity to cytochalasin B indicated the presence of facilitative hexose transport due to hGLUT1 expression. Effect of hGLUT1 on production of 14CO2 from glucose was greater than that of rHKII. Coexpression of the genes did not increase the rate of glucose oxidation compared with expression of hGLUT1 alone.
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PMID:Expression of Human Glucose Transporter Type 1 and Rat Hexokinase Type II Complementary DNAs in Rainbow Trout Embryos: Effects on Glucose Metabolism. 1037 7