Effects of polymer-linked sulfonylurea derivatives on insulin release.

In order to elucidate whether polymerlinked sulfonylurea derivatives may serve as tools to locate the sulfonylurea receptor site, an easily detectable sulfonylurea was synthetized and coupled to cyanogen-bromide activated dextran. The conjugate proved to be unstable and to release sufficient amounts of free agent to explain its insulinotropic activity. Based on these findings previous results claiming that dextran-linked sulfonylureas retain biological activity may be questioned. A stable conjugate was obtained when the acrylyl derivative of the sulfonylurea was co-polymerized with acrylamide. Both a high (greater than 50000) and a low (1500) molecular weight fraction of this conjugate failed to stimulate insulin release from the perfused rat pancreas, questioning the ability of macromolecular conjugates to combine with the sulfonylurea receptor site.