Insulin-like effects of vanadate and selenate on the expression of glucose-6-phosphate dehydrogenase and fatty acid synthase in diabetic rats.
Insulin is capable of regulating cellular and metabolic processes as well as gene expression. In recent years, enthusiasm has surfaced for using insulin-mimetics to study the mechanism of action of insulin. Vanadate and selenate are two compounds that have been found to mimic the action of insulin on control of blood glucose levels in vivo. Vanadate has also been shown to regulate the expression of several enzymes both in vivo and in vitro, however, studies concerning selenate's ability 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 insulin but also positively affects the expression of two key metabolic enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and fatty acid synthase (FAS). Both G6PDH and FAS activity are significantly decreased in diabetic animals compared to non-diabetic control. Treatment of the diabetic animals with either insulin, vanadate or selenate restored both activities to about 80-90% of control. All treatment conditions exhibited activities significantly higher than those determined for the diabetic group but did not differ significantly from each other. Increases in G6PDH or FAS activity are due to increases in mRNA level. Increase in both G6PDH and FAS mRNA was comparable to the observed increase in activity suggesting that regulation of expression by the mimetics occurs pretranslationally.
Berg
E A
EA
Department of Chemistry, Western Michigan University, Kalamazoo 49008, USA.
Wu
J Y
JY
Campbell
L
L
Kagey
M
M
Stapleton
S R
SR
D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental; D005227:Fatty Acids / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D005954:Glucosephosphate Dehydrogenase / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064586:Selenic Acid; D018036:Selenium Compounds / Q000494:pharmacology*; D014638:Vanadates / Q000494:pharmacology*; D015430:Weight Gain
D001786:Blood Glucose; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D018036:Selenium Compounds; D014638:Vanadates; D005954:Glucosephosphate Dehydrogenase; D064586:Selenic Acid