Gluconeogenesis in non-obese diabetic (NOD) mice: in vivo effects of vandadate treatment on hepatic glucose-6-phoshatase and phosphoenolpyruvate carboxykinase.

Abstract

The contribution of gluconeogenesis to hyperglycemia in non-obese diabetic (NOD) mice has been investigated using oral vanadate administration. Vanadate compounds have been shown to mimic many actions of insulin; however, the exact mechanism is poorly understood. The aims of the present study were (1) to elucidate vanadate's action in vivo, and to assess the possibility that its glucose-reducing effect is dependent on the presence of a minimal concentration of insulin; and (2) to evaluate the effects of vanadate administration on the key hepatic gluconeogenesis enzymes, glucose-6-phosphatase (G-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK), as well as glucose-6-phosphate dehydrogenase (G-6-PDH). Vanadate caused a significant reduction in blood glucose but failed to normalize it, despite effective serum vanadate concentrations (26.2 +/- 1.6 micromol/L). Two weeks after initiation of treatment, blood glucose levels were 26.0 +/- 1.8, 21.7 +/- 3.0, 16.0 +/- 1.6, and 14.3 +/- 2.3 mmol/L in the control (C), insulin (I), vanadate (V), and combined vanadate and insulin (V + I) groups, respectively (P < .001). G-6-Pase activity was significantly reduced by vanadate (622 +/- 134 v365 +/- 83 nmol/min/mg protein in C vV, P < .05). PEPCK activity was also significantly reduced (844 +/- 370, 623 +/- 36, 337 +/- 43, and 317 +/- 75 nmol/min/mg in the C, I, V, and V + I groups, respectively, P < .001). No significant differences in the hepatic glycogen stores and G-6-PDH activity were noted between treatment groups. Our study suggests that the inhibition of hepatic G-6-Pase and PEPCK activity by vanadate plays an important role in reducing blood glucose levels in NOD mice.

• Authors: R Mosseri, T Waner, M Shefi, E Shafrir, J Meyerovitch
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 49 Issue 3 Pg. 321-5 (Mar 2000) ISSN: 0026-0495 [Print] United States
• PMID: 10726908 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• Liver Glycogen
• Vanadates
• Glucose-6-Phosphatase
• Phosphoenolpyruvate Carboxykinase (GTP)

Topics

• Animals
• Blood Glucose (drug effects, metabolism)
• Diabetes Mellitus, Type 1 (metabolism)
• Female
• Gluconeogenesis (drug effects)
• Glucose-6-Phosphatase (drug effects, metabolism)
• Liver (enzymology)
• Liver Glycogen (metabolism)
• Mice
• Mice, Inbred NOD
• Phosphoenolpyruvate Carboxykinase (GTP) (drug effects, metabolism)
• Regression Analysis
• Time Factors
• Vanadates (blood, pharmacology)