The present study examined the effects of chronic treatment with
vanadate on in vivo
insulin-stimulated
glucose uptake by various tissues of obese and
insulin-resistant fa/fa rats. It further determined whether the substantial improvement induced by
vanadate administration was associated with altered expression of the
insulin-responsive glucose transporter (GLUT4). Since oral Na3VO4 caused decreases in food intake and
body weight,
vanadate-treated fa/fa rats were compared with controls, fed ad libitum, and pair-fed rats. The animals in the three groups were submitted to hyperinsulinemic clamps combined with the
2-deoxyglucose method. At similar levels of imposed
hyperinsulinemia, the
glucose infusion rate (milligrams per kg.min-1) required to maintain euglycemia, extremely low in controls (0.8 +/- 0.3) and pair-fed rats (1.2 +/- 0.6), was strikingly improved in
vanadate-treated rats (9.5 +/- 0.3). Correspondingly, the
insulin-mediated
glucose utilization indices were 2- to 3-fold higher in all types of muscle in treated rats: hindlimb skeletal muscle, diaphragm, and heart.
Glucose utilization remained unaffected in white adipose tissue and jejunum, whereas it was increased by mere food restriction in brown adipose tissue of pair-fed rats. The amounts of GLUT4 and GLUT4
mRNA were then measured in the
insulin-sensitive tissues of the three groups of animals.
Vanadate treatment induced no change in GLUT4
mRNA or
GLUT4 protein levels in any of the examined tissues. It even prevented the rise in
GLUT4 protein expression caused by calorie restriction in brown adipose tissue of pair-fed rats. In conclusion, chronic administration of
vanadate markedly increases the
insulin-mediated
glucose uptake in muscle of
insulin-resistant fa/fa rats without altering GLUT4 number. A functional improvement of
glucose transporters due to more efficient translocation and/or increased intrinsic activity or changes in the
insulin signaling pathway is, thus, likely to play a major role in the beneficial effects of
vanadate.