Control of hyperglycaemia in diabetic rabbits by a combination of implants

Abstract

Insulin demand varies with meal intake and physical activity. In this study the feasibility of using two implants to meet varying insulin demands was tested in rabbits with alloxan-induced diabetes. One group of severely diabetic rabbits was maintained on a basal dose released by a 50-mg implant made of a compressed admixture of 15% insulin in palmitic acid. The other group of mildly diabetic rabbits required no basal dose implant, but displayed a transient hyperglycaemia as well upon challenge. The supplemental dose was provided by another silicone implant with reservoirs containing 6 mg of compressed insulin. Serous fluid entered the 100μ l internal volume of the silicone implant slowly through an orifice, and dissolved some of the solid insulin. When required, sideways compression of this second implant over the abdominal skin fold of the rabbit delivered the supplemental dose. Typically, a severely diabetic rabbit on a basal dose implant exhibited a transient hyperglycaemia after drinking sweetened water, which raised the blood glucose from 5.4 ± 1.3 mmol l⁻¹ to 14.0 ± 0.5 mmol l⁻¹ for 3 to 4.5 h. In the three test runs, the supplemental bolus of insulin from the silicone implant interrupted the expected rise in blood glucose at 6.1 ± 2.2 mmol l⁻¹ within 1 to 2 h, which then decreased to 3.0 ± 0.2 mmol l⁻¹ for 4 to 5 h before returning to the basal level. A mildly diabetic rabbit showed a blood glucose level of 10.5 ± 1.9 mmol l⁻¹ without the basal dose implant. Its expected transient hyperglycaemia rise to 13.1 ± 0.3 mmol l⁻¹ could also be prevented by the supplemental insulin dose from the silicone implant, and kept at 2.5 ± 0.3 mmol l⁻¹ for 1 to 1.5 h, before returning to the mildly diabetic level in 8 to 9 h. The results demonstrated the feasibility of using an erodible implant to provide a basal insulin dose which could be supplemented by a second implant for better control of transient hyperglycaemia episodes.