Insulinotropic activity of sulfonylurea/pullulan conjugate in rat islet microcapsule.

Abstract

The in vitro long-term effect of a water-soluble sulfonylurea/pullulan conjugate (SUP) on insulinotropic activity and cell viability was investigated using rat pancreatic islets co-entrapped with SUP in conventional alginate-poly(L-lysine) microcapsules. The conjugate was synthesized by coupling a carboxylated glibenclamide derivative to a polysaccharide, pullulan (MW=200,000). In vitro static experiment showed that sulfonylurea concentration in SUP over 50 microM was required to stimulate the rat islets. In a dynamic insulin secretion test, the microcapsules of islets with SUP regained the insulin secretion pattern comparable to that of free islets, while those without SUP showed impaired insulin secretion. The long-term (1 month) culture experiment demonstrated that the microcapsules of islets with SUP, with well-preserved morphology, presented higher insulin secretion level and better ability in responding to glucose changes than those without SUP.