Effects of chronic vanadate administration in the STZ-induced diabetic rat. The antihyperglycemic action of vanadate is attributable entirely to its suppression of feeding.
Vanadate treatment can lower glycemia in diabetic rats. This action is generally attributed to vanadate's insulinomimetic properties, but vanadate also inhibits feeding, which could lower blood glucose. We therefore assessed the contribution of hypophagia to vanadate's antihyperglycemic action in a 3-week study of streptozocin-induced (STZ) diabetic rats. Untreated diabetic rats (n = 8) ate 54% more food than nondiabetic control rats (P < 0.001). Diabetic rats given sodium metavanadate (0.5 mg in 0.5 ml of water by gavage twice daily; n = 8) had significantly lower food intakes (P < 0.001) than untreated diabetic rats. In vanadate-treated diabetic rats, blood glucose levels were significantly lower than in untreated diabetic rats (P < 0.001). Untreated diabetic rats pair-fed to the food intake of the vanadate-treated diabetic rats (n = 8) showed virtually identical blood glucose falls (P > 0.05 vs. vanadate-treated diabetic rats). Vanadate treatment did not affect plasma insulin concentrations in diabetic rats. In nondiabetic rats (n = 8), vanadate treatment significantly reduced food intake (P < 0.05) and also lowered plasma insulin concentrations (P < 0.05) without significantly affecting glycemia. To investigate the mechanism of vanadate's hypophagic effect, we also measured regional hypothalamic levels of neuropeptide Y (NPY), a potent central appetite stimulant that is thought to drive hyperphagia in STZ-induced diabetes. Hypothalamic NPY concentrations rise markedly in diabetes and are normalized by insulin replacement. Unlike insulin, vanadate treatment did not normalize regional hypothalamic NPY concentrations in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Malabu
U H
UH
Department of Medicine, University of Liverpool, United Kingdom.
Dryden
S
S
McCarthy
H D
HD
Kilpatrick
A
A
Williams
G
G
D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001067:Appetite Depressants / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D004327:Drinking Behavior / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008297:Male; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014638:Vanadates / Q000494:pharmacology*
D001067:Appetite Depressants; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D009479:Neuropeptides; D014638:Vanadates