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)

Streptozotocin-induced diabetic (STZ-diabetic) rats were employed to investigate the mechanism(s) whereby myricetin, the active principle of Abelmoschus moschatus (Malvaceae), exerts its glucose-lowering effects. Myricetin was purified from the aerial portion of the plant and administered intravenously. A dose-dependent decrease in plasma glucose concentration was observed 30 min following injection, in parallel with increased plasma beta-endorphin-like immunoreactivity (BER). Myricetin enhanced BER release similarly from isolated adrenal medulla. Plasma glucose-lowering and BER-elevating effects of myricetin were both eliminated after bilateral adrenalectomy. Myricetin failed to lower plasma glucose after treatment with opioid mu-receptor antagonists and in opioid mu-receptor knockout diabetic mice. Injection of myricetin three times daily for three consecutive days resulted in increased expression of the glucose transporter subtype 4 (GLUT 4) in soleus muscle and in reduced expression of phosphoenolpyruvate carboxykinase (PEPCK) in liver; these inductions were preventable by opioid mu-receptor blockade. Findings support the conclusion that the plasma glucose-lowering action of myricetin in insulin-deficient animals is mediated by activation of opioid mu-receptors of peripheral tissues in response to increased beta-endorphin secretion. Opioid mu-receptor activation is held responsible for the enhancement of muscle GLUT 4 gene expression and the attenuation of hepatic PEPCK gene expression observed in these myricetin-treated diabetic animals.
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PMID:Mediation of beta-endorphin by myricetin to lower plasma glucose in streptozotocin-induced diabetic rats. 1620 17

Dioxins and dioxin-like compounds encompass a group of structurally related heterocyclic compounds that bind to and activate the aryl hydrocarbon receptor (AhR). The prototypical dioxin is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic industrial byproduct that incites numerous adverse physiological effects. Global commercial production of the structurally similar polychlorinated biphenyls (PCBs), however, commenced early in the 20(th) century and continued for decades; dioxin-like PCBs therefore contribute significantly to total dioxin-associated toxicity. In this study, PCB 126, the most potent dioxin-like PCB, was evaluated with respect to its direct effects on hepatic glucose metabolism using primary mouse hepatocytes. Overnight treatment with PCB 126 reduced hepatic glycogen stores in a dose-dependent manner. Additionally, PCB 126 suppressed forskolin-stimulated gluconeogenesis from lactate. These effects were independent of acute toxicity, as PCB 126 did not increase lactate dehydrogenase release nor affect lipid metabolism or total intracellular ATP. Interestingly, provision of cells with glycerol instead of lactate as the carbon source completely restored hepatic glucose production, indicating specific impairment in the distal arm of gluconeogenesis. In concordance with this finding, PCB 126 blunted the forskolin-stimulated increase in phosphoenolpyruvate carboxykinase (PEPCK) mRNA levels without affecting glucose-6-phosphatase expression. Myricetin, a putative competitive AhR antagonist, reversed the suppression of PEPCK induction by PCB 126. Furthermore, other dioxin-like PCBs demonstrated similar effects on PEPCK expression in parallel with their ability to activate AhR. It therefore appears that AhR activation mediates the suppression of PEPCK expression by dioxin-like PCBs, suggesting a role for these pollutants as disruptors of energy metabolism.
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PMID:PCB 126 and other dioxin-like PCBs specifically suppress hepatic PEPCK expression via the aryl hydrocarbon receptor. 2261 11