Incorporation of sulfonylurea into sugar-carrying polymers and their effects on insulin secretion from MIN6 cells in a solution state.

A hypoglycemic sulfonylurea (SU) was incorporated into non-reducing glucose-bearing polystyrene (PS) derivative for enhanced interaction with, and insulin secretion from an insulinoma cell line (MIN6). SU derivative was copolymerized with styrene having sugar moiety such as maltose or lactose. About an 80% increase in insulin secretion for poly(N-p-vinylbenzyl-D-maltonamide-co-SU) (p(VMA-co-SU)) was observed when the copolymer was added to the culture medium (SU: 25 mol%). whereas about 50% increase for poly(N-p-vinylbenzyl-D-lactonamide-co-SU) (p(VLA-co-SU)) was observed when compared with unstimulated cells. From the measurement of flow cytometry, the fluorescence intensity of MIN6 cells incubated in culture media containing FITC-labeled SU-incorporated copolymer increased remarkly owing to specific interaction between receptors in the cell membrane and SU ligands in the copolymer. When sugar and/or SU-incorporated copolymer were co-entrapped with the cells in agarose or collagen gel as an extracellular matrix for three-dimensional culture. p(VMA-co-SU) enhanced more insulin secretion from MIN6 cells than other polymers and it was found that collagen gel was more effective in insulin secretion than agarose