Incorporation of sulfonylurea into N-isopropylacrylamide as an extracellular matrix for an artificial pancreas

High-molecular-weight N-isopropylacrylamide copolymers with small amounts o f sulfonylurea (SU, typically 2-4 mol % in the feed) were synthesized by fr ee radical polymerization in benzene. SU-incorporated polymer solutions (5, 6, 8, and 10% w/v) in a culture medium (pH 7.4, 0.15 m ionic strength) wit h islet cells were mixed and poured into Millicells which supported gel for mation. In order to increase the gelation temperature, the SU-incorporated copolymer gel, p(NiPAAmco-SU), was blended with the p(NiPAAm-co-AAc) polyme r at a ratio of 4 to 96. Interaction between the islet cells and the synthe tic matrix of SU-incorporated copolymer gel resulted in effective cell viab ility and such cell functions as insulin secretion. To verify the specific interaction between the SU (K+ channel closer)-incorporated copolymer and i slet cells, the cells were pretreated with diazoxide, an agonist of the ATP -sensitive K+ channel (K+ channel opener), before interaction between the p olymer and islet cells. This treatment suppressed the action of SU on the i slet cells. The results from this study provide evidence that the SU-incorp orated copolymer stimulated insulin secretion by specific interaction betwe en SU moieties in the polymer and the islet cells.