Mechanisms by which bis(maltolato)oxovanadium(IV) normalizes phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression in streptozotocin-diabetic rats in vivo.
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.
Marzban
Lucy
L
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
Rahimian
Roshanak
R
Brownsey
Roger W
RW
McNeill
John H
JH
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology*; D015870:Gene Expression / Q000187:drug effects*; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D010695:Phlorhizin / Q000494:pharmacology; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics*; D011753:Pyrones / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014638:Vanadates / Q000494:pharmacology* / Q000627:therapeutic use
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D011753:Pyrones; D012333:RNA, Messenger; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates; D010695:Phlorhizin; D005952:Glucose-6-Phosphatase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)