Insulin Sensitivity and Glucose Effectiveness in Long-Term Islet-Autotransplanted Dogs

Parameters determining glucose tolerance were quantified with Bergman's minimal-model method applied to frequently sampled intravenous glucose tolerance tests in five normal and five islet-autotransplanted mongrel dogs 8–10 mo posttransplantation. Despite normal fasting glucose and insulin levels, glucose tolerance was reduced in the islet-transplanted dogs (1.5 ± 0.4 vs. 4.2 ± 0.4%/min in normal controls, P < .002). The reduction in glucose tolerance was due to a reduced insulin response to glucose injection (4 ± 1 vs. 32 ± 5 μU/ml, P < .001) and reduced glucose effectiveness (1.7 ± 0.5 vs. 5.3 ± 0.6 × 10² min⁻¹, P < .005) but not to a reduction in insulin sensitivity (8.4 ± 0.6 vs. 7.8 ± 0.7 × 10⁴ min⁻¹ · μU⁻¹ · ml⁻¹, P > .5). Our results suggest that reduced insulin secretory response as a result of islet transplantation may result in a defect in glucose's ability to promote its own disposal but not necessarily in a defect in insulin sensitivity.