Mechanisms by which bis(maltolato)oxovanadium(IV) normalizes phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression in streptozotocin-diabetic rats in vivo.

Abstract

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.

• Authors: Lucy Marzban, Roshanak Rahimian, Roger W Brownsey, John H McNeill
• Journal: Endocrinology (Endocrinology) Vol. 143 Issue 12 Pg. 4636-45 (Dec 2002) ISSN: 0013-7227 [Print] United States
• PMID: 12446591 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Insulin
• Pyrones
• RNA, Messenger
• bis(maltolato)oxovanadium(IV)
• Vanadates
• Phlorhizin
• Glucose-6-Phosphatase
• Phosphoenolpyruvate Carboxykinase (GTP)

Topics

• Animals
• Blood Glucose (metabolism)
• Diabetes Mellitus, Experimental (drug therapy, enzymology)
• Gene Expression (drug effects)
• Glucose-6-Phosphatase (genetics)
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Insulin (blood, therapeutic use)
• Kidney (enzymology)
• Liver (enzymology)
• Male
• Phlorhizin (pharmacology)
• Phosphoenolpyruvate Carboxykinase (GTP) (genetics)
• Pyrones (pharmacology, therapeutic use)
• RNA, Messenger (analysis)
• Rats
• Rats, Wistar
• Vanadates (pharmacology, therapeutic use)