Preserved pulsatile insulin release from prediabetic mouse islets

During the development of type I diabetes, the plasma insulin pattern chang es. Because the islet secretory pattern has been implicated in this phenome non, insulin release was measured from female nonobese diabetic (NOD) mouse islets isolated at different ages. Islets from 5-week-old mice were used a s controls because they had no infiltrating mononuclear cells and insulin r elease rose almost g-fold with maintained oscillatory frequency when the gl ucose concentration was raised from 3 to 11 mM. Islets isolated from 13- an d 25-week-old mice were infiltrated with mononuclear cells. In these islets , increase in the glucose concentration from 3 to 11 mM only doubled insuli n release. However, despite the cellular infiltration, insulin release was pulsatile. Islets from 13-week-old mice had reduced glucose oxidation rate. Culture of such islets for 7 days at 11.1 mM glucose causes a decrease in the number of mononuclear cells infiltrating the islets, which in the prese nt study was accompanied by a normalization of both glucose oxidation and g lucose-induced insulin release. In the presence of the mitochondrial substr ate alpha-keto-isocaproate (5 mM) both control and infiltrated islets respo nded with pronounced insulin pulses with similar amplitudes. The results su ggest that the deranged plasma insulin pattern observed during the developm ent of type I diabetes may be related to decrease in the insulin pulse ampl itude rather than loss of the pulsatile release from the islets.