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 structural modification of insulin results in the generation of insulin analogues that show altered binding affinities to the insulin receptor and/or the IGF-I receptor, and as a consequence insulin analogues may have altered mitogenic potency. We analysed the proliferative effect of the rapid-acting insulin analogue Apidra (insulin glulisine) on mammary epithelial cells. We show that Apidra and Actrapid (recombinant human insulin) have similar proliferative effects on benign MCF10A and tumorigenic MCF7 cells and on epithelial cells of mouse mammary gland. Whereas Apidra and Actrapid induced similar activation of Erk1/2, activation of Akt/PKB by Apidra was significantly weaker compared to regular insulin. As AKT/PKB, an effector of the phosphoinositide 3-kinase pathway, mediates metabolic effects of insulin, we studied induction of hexokinase-2 in MCF7 cells and hexokinase-2 and hexokinase-4 in HepG2 cells by Actrapid and Apidra. Both genes were not significantly induced by Actrapid and Apidra in these cell lines.
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PMID:Proliferative effect of Apidra (insulin glulisine), a rapid-acting insulin analogue on mammary epithelial cells. 1948 May 64

Women with type 1 diabetes are subfertile. Diabetes negatively affects pregnancy by causing early miscarriage and poor prenatal outcomes. In this study we examine consequences of maternal type 1 diabetes on early embryo development, metabolic gene expression, and the pattern of insulin receptor (IR) and IGF-I receptor (IGF-IR) distribution in rabbit blastocysts. In female rabbits, type 1 diabetes was induced by alloxan treatment. Six-day-old blastocysts were recovered and assessed for receptor distribution and metabolic gene expression. In vitro culture of blastocysts was performed in medium containing 1 mm, 10 mm, or 25 mm glucose, simulating normo- and hyperglycemic developmental condition in vitro. The fertility rate of the diabetic rabbits clearly mirrored subfertility with a drop in blastocyst numbers by 40% (13.3 blastocysts in diabetic vs. 21.9 in control females). In blastocysts onset and progression of gastrulation was delayed and expression of IR and IGF-IR and their metabolic target genes (hexokinase, phosphoenolpyruvate carboxykinase), both in vivo and in vitro, was down-regulated. The amount of apoptotic cells in the embryonic disc was increased, correlating closely with the reduced transcription of the bcl-x(L) gene. Blastocyst development is clearly impaired by type 1 diabetes during early pregnancy. Insulin-stimulated metabolic genes and IR and IGF-IR are down-regulated, resulting in reduced insulin and IGF sensitivity and a delay in development. Dysregulation of the IGF system and embryonic glucose metabolism are potential reasons for diabetogenous subfertility and embryopathies and start as soon as during the first days of life.
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PMID:Maternal diabetes impairs gastrulation and insulin and IGF-I receptor expression in rabbit blastocysts. 2063 Oct