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)

This short review describes the role of progesterone in the insulin-resistance of pregnancy and the present knowledge of the intracellular mechanisms of action of the steroid in carbohydrate metabolism of female rat adipocytes. Observations concerning steroid effects on the binding of insulin to its specific receptors are often contradictory, and depend on cells used to study it. It is now generally accepted that, in isolated adipocytes, the decreased responsiveness to insulin produced by progesterone is due to a post-receptor effect. Furthermore, basal glucose metabolism (in the absence of insulin) is decreased by progesterone treatment and by the acute effect of progesterone when added directly into the incubation medium. Progesterone induces an intrinsic post-receptor effect which is related to decreased phosphorylation of glucose by hexokinase but has no effect on glucose transport. The effect on hexokinase activity is an indirect one taking place either before or after activation of the enzyme. During the last decade, a large body of evidence (Xenopus oocytes and other cells) indicates that steroids interact with the cell surface rather than penetrating the cell and interacting exclusively with a nuclear receptor. The second messengers, such as cyclic AMP and calcium, play a major role in this non-genomic mechanism. The direct and rapid effect (20 min.) of progesterone in adipocytes supports the non-genomic mechanism of action; there is neither any lag period prior to the appearance of the physiological response nor any inhibition of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Carbohydrate metabolism of female rat adipocytes: effects and mechanisms of action of progesterone. 381 56

Progesterone decreases the oxidation of 2-deoxyglucose and glucose through the pentose-phosphate pathway in isolated female rat adipocytes and, therefore, the effect of this steroid incubation in vitro, progesterone decreased total hexokinase activity but did not affect the isoenzyme-I activity. Progesterone had no direct effect on fat cell cytosol hexokinase and its action on glucose oxidation was not affected by variations in the concentration of Mg2+, the cofactor of hexokinase. Our data suggest that the decreased activity of hexokinase in the presence of progesterone is due to a decrease in the activity of the insulin-sensitive isoenzyme-II. This results from the steroid acting at a step beyond enzyme activation and may be mediated by a feedback mechanism.
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PMID:Progesterone and glucose metabolism in the female rat adipocyte: effect on hexokinase activity. 717 24

A clearer understanding of biochemical properties of oocytes and embryos and their changes in oocyte maturation and embryonic development may have significant clinical implications, especially for in vitro fertilization techniques. Microtechniques and highly sensitive methods such as enzymatic cycling, micro-Western analysis, reverse transcription polymerase chain reaction and so on were employed to study these processes. Low hexokinase activity and high activities of enzymes in the phosphate pathway were characteristic of immature oocytes. During maturation, the activities of hexokinase and phosphofructokinase increased significantly. These changes were used to analyze involvement of epidermal growth factor (EGF) and prostaglandins (PG) in oocyte maturation. EGF is shown to stimulate maturation by increasing PG production in granulosa cells. Electrophysiologically, the sensitivity of oocyte to inositol triphosphate increased and Ca2+ release system developed during maturation. Progesterone production of oocyte and embryos are shown by enzymatic cycling and other methods using radiometry. This hormone produced by embryos themselves may play a role in embryonic development in intracrine fasion. There is 100-fold increase in glucose uptake from oocyte to blastocyst in mice. A switch in substrate preference of the embryo from pyruvate to glucose during preimplantation development may be explained by increases in the activity of hexokinase and expression of glucose transporter, GLUT1. Hexokinase activities determined by NADP cycling increased 20-fold while expression of GLUT1 assessed by micro-Western method 10-fold. GLUT1 expression was also analyzed by RT-PCR, which indicated that the expression is regulated at transcription level. There is a delay in the developmental changes in glucose uptake, hexokinase activity and GLUT1 expression when the embryos are developed in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Studies in oocyte maturation and embryonic development]. 837 Oct 11