Insulin-mimetic agents vanadate and pervanadate stimulate glucose but inhibit amino acid uptake.

Abstract

The protein tyrosine phosphatase (PTP) inhibitors vanadate and pervanadate (pV) exert insulin-like biologic effects. In cultured differentiated rat L6 skeletal muscle cells, vanadate and pV stimulated 2-deoxy-D-[3H]glucose uptake in a dose- and time-dependent manner. There was no increase in maximum stimulation by additional insulin. In contrast, whereas 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 a decrease in transporter affinity and a small decrease in maximum transport capacity, whereas the insulin-stimulated increase in maximum transport capacity 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.

• Authors: E Tsiani, N Abdullah, I G Fantus
• Journal: The American journal of physiology (Am J Physiol) Vol. 272 Issue 1 Pt 1 Pg. C156-62 (Jan 1997) ISSN: 0002-9513 [Print] United States
• PMID: 9038821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids
• Drug Combinations
• Enzyme Inhibitors
• Hypoglycemic Agents
• Insulin
• pervanadate
• beta-Alanine
• 2,2-dimethyl-beta-alanine
• Vanadates
• Ouabain
• Cycloheximide
• Deoxyglucose
• Protein Tyrosine Phosphatases
• Glucose

Topics

• Amino Acids (antagonists & inhibitors, pharmacokinetics)
• Animals
• Carcinoma, Hepatocellular (metabolism, pathology)
• Cell Line
• Cycloheximide (pharmacology)
• Deoxyglucose (pharmacokinetics)
• Drug Combinations
• Enzyme Inhibitors (pharmacology)
• Glucose (pharmacokinetics)
• Hypoglycemic Agents (pharmacology)
• Insulin (pharmacology)
• Muscle, Skeletal (cytology, metabolism)
• Ouabain (pharmacology)
• Protein Tyrosine Phosphatases (antagonists & inhibitors)
• Rats
• Vanadates (pharmacology)
• beta-Alanine (analogs & derivatives, pharmacokinetics)