Synthetic Insulin Mediators as Therapeutic Agents

Insulin's action on specific transmembrane receptors releases low molecular weight substanceswhich exhibit remarkable insulin mimetic properties. This data indicates that insulin resistance couldlikely be a post-receptor defect since these low molecular weight substances mediate insulin's actionon the cell or in vivo. These mediators are inositol phosphoglycan linkers positioned between the cellmembrane and extracellular proteins. Purification of these mediators yields oligosaccharides of twodistinct classes; one contains mannose, glucosamine and myoinositol and the other contains mannose,galactosamine, and D-chiroinositol (DCI). Synthetic derivatives of galactosamine-DCI dimers demonstratelow level bioactivity vis-a-vis the actual mediators itself. A synthetic drug fashioned after the insulinmediator could be a treatment directed at insulin resistance and those conditions arising from thisdisorder including 5 million or so NIDDM sufferers in the U.PS. The synthesis of the oligosaccharideswill follow a scheme in which a stereoselective glycosidation reaction is the key step. These syntheticmaterials will be tested with in vitro and in vivo bioassays to determine their drug potential.