INSULIN-MIMETIC AGENTS VANADATE AND PERVANADATE STIMULATE GLUCOSE BUTINHIBIT AMINO-ACID-UPTAKE

The protein tyrosine phosphatase (PTP) inhibitors vanadate and pervana date (pV) exert insulin-like biologic effects. In cultured differentia ted rat L6 skeletal muscle cells, vanadate and pV stimulated 2-deoxy-D -[H-3]glucose uptake in a dose- and time-dependent manner. There was n o increase in maximum stimulation by additional insulin. In contrast, whereas insulin stimulated [C-14]methylaminoisobutyric acid (MeAIB) up take, basal uptake was inhibited by vanadate and pV. Insulin-stimulate d MeAIB uptake was also inhibited in a dose-dependent manner and compl etely abolished by 5 mM vanadate or 0.1 mM pV. The inhibitory effect o n basal MeAIB uptake was associated with a decrease in transporter aff inity and a small decrease in maximum transport capacity, whereas the insulin-stimulated increase in maximum transport capacity was complete ly inhibited. Inhibition of MeAIB uptake by vanadate and pV was not bl ocked by cycloheximide, and oubain did not inhibit uptake. Vanadate al so inhibited amino acid deprivation-stimulated MeAIB uptake. Insulin-s timulated 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.