The insulin-mimetic agents vanadate and pervanadate stimulate
glucose but inhibit amino acid uptake.
Tsiani, E., N. Abdullah, and I. G. Fantus.
Department of Medicine, Mount Sinai Hospital, the Department of
Physiology and Banting and Best Diabetes Centre, University of
Toronto, Toronto, Ontario Canada
APStracts 3:0269C, 1996.
The protein tyrosine phosphatase (PTP) inhibitors vanadate and
pervanadate (pV) exert insulin-like biological effects. In cultured
differentiated rat L6 skeletal muscle cells vanadate and pV
stimulated 2-Deoxy-D-[3H]-glucose (2DG) uptake in a dose and time
-dependent manner. There was no increase in maximum stimulation by
additional insulin. In contrast, while insulin stimulated 14C
-methylaminoisobutyric acid (MeAIB) uptake, basal uptake was inhibited
by vanadate and pV. Insulin-stimulated MeAIB uptake was also
inhibited in a dose-dependent manner and completely abolished by 5 mM
vanadate or 0.1 mM pV. The inhibitory effect on basal MeAIB uptake
was associated with an increase in Km and a small decrease in Vmax
while the insulin-stimulated increase in Vmax was completely
inhibited. Inhibition of MeAIB uptake by vanadate and pV was not
blocked by cycloheximide and oubain did not inhibit uptake. Vanadate
also inhibited amino acid deprivation -stimulated MeAIB uptake.
Insulin-stimulated MeAIB uptake was also inhibited in rat hepatoma
cells. Thus vanadate and pV mimic insulin to stimulate glucose uptake
but inhibit system A amino acid uptake. The relative inhibitory
concentrations of vanadate and pV suggest that the mechanism may
involve PTP inhibition.
Received 30 May 1996; accepted in final form 9 August 1996.
APS Manuscript Number C316-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996