EFFECTS OF VANADIUM ON INSULIN TARGET TISSUES

DESCRIPTION: (Principal Investigator's Abstract): Vanadium is
increasingly a source of possible toxic effects through the use of fossil
fuels and its incorporation into metal alloys. Vanadium in the form of
vanadate has been shown to have a number of insulin-mimetic properties when
given acutely in vitro. However, the effects of chronic administration on
insulin sensitive tissues in vivo is much less well studied. Therefore,
the overall purpose of this proposal is to examine the effects of vanadium
on insulin-sensitive activities at its target cell sites. The specific
objectives are: 1) to determine if vanadate or vanadyl is preferentially
accumulated and retained in tissues with insulin-sensitive glucose
transport systems; 2) to determine if vanadium alters insulin receptor
numbers, binding, or function; 3) to determine if vanadium has effects on
insulin-stimulated activities in target tissues; and 4) to determine if
vanadium affects insulin metabolism. Rats will be given vanadium, as
sodium orthvanadate or vanadyl sulfate, in a liquid diet and a number of
insulin-sensitive activities of target tissues measured and compared to
control animals. Specifically, various organs will be harvested and the
vanadium content determined by neutron activation analysis. Hepatocytes
and adipocytes will be isolated from animals and insulin binding analyzed
by Scatchard plots. Receptor function will be assessed by assaying its
tyrosine kinase activity. Isolated hepatocytes will be assayed for the
insulin-sensitive activities of: amino acid transport, inhibition of
protein degradation, and glucose incorporation in glycogen. Isolated
adipocytes will be assayed for the insulin-sensitive activities of:
glucose uptake, glucose incorporation into lipids, glucose oxidation, and
anti-lipolysis. Finally, insulin degradation will be studied in perfused
liver and isolated hepatocytes to determine if vanadium alters its
metabolism. Those studies will allow determination of the effect of
vanadium on insulin target tissue and begin analysis of its mechanisms of
action.