Research Project
2147564
Insulin's action on specific transmembrane receptors releases low molecular weight substances which exhibit remarkable insulin mimetic properties. This data indicates that insulin resistance could likely be a post-receptor defect since these low molecular weight substances mediate insulin's action on the cell or in vivo. These mediators are inositol phosphoglycan linkers positioned between the cell membrane and extracellular proteins. Purification of these mediators yields oligosaccharides of two distinct classes; one contains mannose, glucosamine and myoinositol and the other contains mannose, galactosamine, and D-chiroinositol (DCI). Synthetic derivatives of galactosamine-DCI dimers demonstrate low level bioactivity vis-a-vis the actual mediators itself. A synthetic drug fashioned after the insulin mediator could be a treatment directed at insulin resistance and those conditions arising from this disorder including 5 million or so NIDDM sufferers in the U.PS. The synthesis of the oligosaccharides will follow a scheme in which a stereoselective glycosidation reaction is the key step. These synthetic materials will be tested with in vitro and in vivo bioassays to determine their drug potential.
