Complex organisms use chemical signals, e.g., hormones and growth factors, to integrate and coordinate the function of specialized tissues. Information is transferred to target cells when chemical signals bind to specific surface receptors and, as a result, cell structure and function can be profoundly altered. To study how information flows to metabolic control points, we have developed a powerful experimental system, consisting of a giant cell (amphibian oocyte), parafin oil-based cell microinjection and microdissection procedures and single cell analyses. Experiments have focussed on certain heavy metals (vanadate, pervanadate, Hg++, Cd++, and Zn++), which at low concentrations act as insulin mimics, but bypass the insulin receptor. Since these chemicals are potent phosphatase inhibitors in vitro, it has been assumed that they act by blocking the action of intracellular phosphatases involved in signal transduction. Consistent with this, our microinjection studies have shown that vanadate, pervanadate and HgCl2 stimulate hexose uptake by acting at intracellular sites. HgCl2 appears to stimulate hexose uptake through changes in cell volume, and similar stimulation is seen when cells are osmotically swelled. In contrast, these insulin mimics (and insulin through its receptor) stimulate protein synthesis by acting at the cell surface where they cause a rapid, net influx of Mg. The resulting increase in intracellular Mg stimulates translation, which is exquisitely sensitive to that divalent cation. Future plans include: 1) characterizing further the detailed mechanisms by which insulin mimics affect the function of oocytes and somatic cells, 2) examining the role of intracellular Mg in metabolic control, and 3) determining if inappropriate cellular signalling is an unappreciated toxic effect of heavy metals that have insulin-like actions.
