Ea. Berg et al., INSULIN-LIKE EFFECTS OF VANADATE AND SELENATE ON THE EXPRESSION OF GLUCOSE-6-PHOSPHATE-DEHYDROGENASE AND FATTY-ACID SYNTHASE IN DIABETIC RATS, Biochimie, 77(12), 1995, pp. 919-924
Insulin is capable of regulating cellular and metabolic processes as w
ell as gene expression. In recent years, enthusiasm has surfaced for u
sing insulin-mimetics to study the mechanism of action of insulin. Van
adate and selenate are two compounds that have been found to mimic the
action of insulin on control of blood glucose levels in vivo. Vanadat
e has also been shown to regulate the expression of several enzymes bo
th in vivo and in vitro, however, studies concerning selenate's abilit
y to regulate expression have not been reported. In this study we show
that administration of vanadate or selenate to streptozotocin-induced
diabetic rats not only normalizes blood glucose levels similarly to i
nsulin but also positively affects the expression of two key metabolic
enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and fatty acid syn
thase (FAS). Both G6PDH and FAS activity are significantly decreased i
n diabetic animals compared to non-diabetic control. Treatment of the
diabetic animals with either insulin, vanadate or selenate restored bo
th activities to about 80-90% of control. All treatment conditions exh
ibited activities significantly higher than those determined for the d
iabetic group but did not differ significantly from each other. Increa
ses in G6PDH or FAS activity are due to increases in mRNA level. Incre
ase in both G6PDH and FAS mRNA was comparable to the observed increase
in activity suggesting that regulation of expression by the mimetics
occurs pretranslationally.