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

Liver insulin resistance and glucagon-stimulated hepatic glucose production are characteristics of the diabetic state. To determine the potential role of glucose toxicity in these abnormalities, we examined whether phlorizin treatment of streptozotocin-diabetic rats resulted in altered expression of genes involved in key steps of hepatic glucose metabolism. By inhibiting renal tubular glucose reabsorption, phlorizin infusion to diabetic rats induced normoglycaemia, did not significantly alter low circulating insulinaemia, but caused a marked decrease in hyperglucagonaemia. Glucokinase and L-type pyruvate kinase mRNA levels were reduced respectively by 90% and 70% in fed diabetic rats, in close correlation with changes in enzyme activities. Eighteen days of phlorizin infusion partially restored glucokinase mRNA and activity (40% of control levels), but had no effect on L-type pyruvate kinase mRNA and activity. In contrast to the glycolytic enzymes, mRNA and activity of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase were increased (10- and 2.2-fold, respectively) in fed diabetic rats. Phlorizin administration decreased phosphoenolpyruvate carboxykinase mRNA to values not different from those in control rats, while phosphoenolpyruvate carboxykinase activity remained 50% higher than that in control rats. The 50% rise in liver glucose transporter (GLUT 2) mRNA and protein, produced by diabetes, was also corrected by phlorizin treatment. In conclusion, we propose that phlorizin treatment of diabetic rats may induce a partial shift of the predominating gluconeogenesis, associated with hepatic glucose overproduction, into glycolysis, by correction of impaired pre-translational regulatory mechanisms. This could be essentially mediated through improved pancreatic alpha-cell function and subsequent lowering of hyperglucagonaemia. These observations suggest that glucagon-stimulated hepatic glucose production may result, in part, from glucose toxicity.
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PMID:Phlorizin treatment of diabetic rats partially reverses the abnormal expression of genes involved in hepatic glucose metabolism. 847 72

Vanadium treatment normalizes plasma glucose levels in streptozotocin-diabetic rats in vivo, but the mechanism(s) involved are still unclear. Here, we tested the hypothesis that the in vivo effects of vanadium are mediated by changes in gluconeogenesis. Diabetic rats were treated with bis(maltolato)oxovanadium(IV) (BMOV) in the drinking water (0.75-1 mg/ml, 4 wk) or, for comparison, with insulin implants (4 U/d) for the final week of study. As with insulin, BMOV lowered plasma glucose and normalized phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) mRNA in the liver and kidney of diabetic rats. To determine the importance of reducing hyperglycemia per se, diabetic rats were treated either with a single ED(50) dose of BMOV (0.1 mmol/kg, ip) or with phlorizin (900 mg/kg.d, 5 d). BMOV rapidly restored PEPCK and G-6-Pase mRNA and normalized plasma glucose in responsive (50%) diabetic rats but had no effect on the nonresponsive hyperglycemic rats. Phlorizin corrected plasma glucose but had no effect on PEPCK mRNA and only partially normalized G-6-Pase mRNA. In conclusion, 1) BMOV inhibits PEPCK mRNA expression and activity by rapid mechanisms that are not reproduced simply by correction of hyperglycemia; and 2) BMOV inhibits G-6-Pase expression by complex mechanisms that depend, in part, on correction of hyperglycemia.
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PMID:Mechanisms by which bis(maltolato)oxovanadium(IV) normalizes phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression in streptozotocin-diabetic rats in vivo. 1244 91

Gluconeogenic capacity may be an important factor regulating dry matter intake (DMI) in lactating dairy cows. To determine whether increased glucose demand affects feed intake and hepatic gene expression, lactating Holstein cows were treated with phlorizin or vehicle (propylene glycol) for 7 d. Multiparous cows (n = 12; 269 +/- 65 d in milk, mean +/- SD) were randomly assigned to treatment sequence in a crossover design and were adapted to a common diet for 7 d before the beginning of the experiment. Phlorizin injected s.c. at 4 g/d caused glucose excretion in urine at the rate of 474 g/d. Although phlorizin decreased lactose synthesis and milk production (both P < 0.01), DMI and 3.5% fat-corrected milk production were not altered by treatment. A net deficit of 383 g glucose/d in milk and urine for phlorizin (relative to control) was likely replaced partially through increased gluconeogenesis. The molar insulin:glucagon ratio was decreased 17% by phlorizin (P < 0.001) and hepatic phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and pyruvate carboxylase mRNA abundance increased (all P < 0.05). Late-lactation dairy cows adapted quickly to an increase in peripheral glucose demand; adaptation mechanisms likely included enhanced gluconeogenic capacity, whereas DMI was not altered.
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PMID:Phlorizin administration increases hepatic gluconeogenic enzyme mRNA abundance but not feed intake in late-lactation dairy cows. 1614 Aug 99