In an attempt to develop a totally synthetic, self-regulated insulin delivery system to treat diabetes, N-substituted poly(acrylamide) copolymer gels bearing boronate functionality have been chemically optimized so as to undergo an abrupt and glucose dependent change in hydration. This study highlights an importance of fine-tuning the mesh size of the gel relative to that of insulin in order to achieve the better controlled-release in a manner less sensitive to the temperature, even with an apparently marginal change of hydration.