Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
 4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) catalyses the interconversion of active corticosterone and inert 11-dehydrocorticosterone. 11beta-HSD-1 is highly expressed in liver, where the reaction direction is 11beta-reduction, thus potentially increasing intrahepatic active glucocorticoid levels. Inhibition of 11beta-HSD-1 increases insulin sensitivity in humans in vivo suggesting that hepatic 11beta-HSD-1 plays a role in the maintenance or control of key glucocorticoid-regulated metabolic functions. We have selectively repressed hepatic 11beta-HSD-1 in rats by oestradiol administration for 42 days. This nearly completely repressed hepatic 11beta-HSD-1 mRNA expression and enzyme activity and reduced expression of hepatic glucocorticoid-inducible genes including phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting step in gluconeogenesis. Similar effects were seen after 3 weeks of oestradiol treatment. To examine whether this was due to any direct effect of oestradiol upon PEPCK, the experiment was repeated in adrenalectomised rats+/-glucocorticoid replacement. In adrenalectomised rats, oestradiol did not attenuate hepatic PEPCK, whilst glucocorticoid replacement restored this action. Oestradiol did not alter hepatic metabolism of corticosterone by pathways other than 11beta-HSD-1. These data suggest 11beta-HSD-1 plays an important role in maintaining expression of key glucocorticoid-regulated hepatic transcripts. Enzyme inhibition may provide a useful therapeutic target for manipulating glucose homeostasis.
 ...
PMID:Interactions between oestradiol and glucocorticoid regulatory effects on liver-specific glucocorticoid-inducible genes: possible evidence for a role of hepatic 11beta-hydroxysteroid dehydrogenase type 1. 985 82