Chronic glucose-lowering effects of rosiglitazone and bis(ethylmaltolato)oxovanadium(IV) in ZDF rats.
The aim of this study was to determine if there was a synergistic or additive effect of a thiazolidinedione derivative (rosiglitazone (ROS)) and a vanadium compound (bis(ethylmaltolato)oxovanadium(IV) (BEOV)) on plasma glucose and insulin levels following chronic oral administration to Zucker diabetic fatty (ZDF) rats. Whole-blood vanadium levels were determined at time 0 and at days 1, 6, and 18. The doses of BEOV (0.1 mmol/kg) and ROS (2.8 micromol/kg) were selected to produce a glucose-lowering effect in 30% (ED30) of animals. Both drugs were administered daily by oral gavage as suspensions in 1% carboxymethylcellulose (CMC) in a volume of 2.5 mL/kg. The total volume administered to all rats was 5 mL/(kg.day). The combination of BEOV and ROS was effective in lowering plasma glucose levels to <9 mmol/L in 60% of fatty animals as compared with 30% for BEOV and 10% for ROS alone. The age-dependent decrease in plasma insulin levels associated with beta-cell failure in the ZDF rats did not occur in the BEOV-treated fatty groups. There was no effect of any treatment on body weight; however, there was a significant reduction in both food and fluid intake in fatty groups treated with BEOV. There were no overt signs of toxicity and no mortality in this study. Both BEOV and ROS were effective in lowering plasma glucose levels, as stated above, and there was at least an additive effect when BEOV and ROS were used in combination.
Yuen
Violet G
VG
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
Bhanot
Sanjay
S
Battell
Mary L
ML
Orvig
Chris
C
McNeill
John H
JH
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D007328:Insulin / Q000097:blood; D007441:Intubation, Gastrointestinal; D008297:Male; D011753:Pyrones / Q000008:administration & dosage*; D051381:Rats; D011924:Rats, Zucker; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*; D014638:Vanadates / Q000008:administration & dosage*
D001786:Blood Glucose; D007328:Insulin; D011753:Pyrones; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates