Oscillatory Insulin Secretion After Pancreas Transplant

In vivo studies of β-cell secretory function have demonstrated the existence of rapid insulin oscillations of small amplitude recurring every 8–15 min in normal subjects. This study evaluated the effects of pancreas transplant on rapid insulin oscillations. Samples for glucose, insulin, and C-peptide were drawn during constant glucose infusion at 2-min intervals for 90 min from six successful Px patients with type I diabetes mellitus, from six normal nondiabetic control subjects, and from three Kx subjects. A computerized algorithm (ULTRA) was used for pulse detection. In the Px group, the average insulin pulse period was significantly shorter than in both the control and Kx groups (Px 8.1 ± 0.5, control 12.5 ± 0.7, Kx 12.4 ± 0.5 min, P < 0.0005). By contrast, the C-peptide pulse periods (Px 16.8 ± 2.3, control 14.7 ± 1.2, Kx 15.3 ± 1.5 min) were similar in the three groups. Spectral analysis confirmed that the frequency of the insulin pulses was increased in the Px group. The absolute amplitude of the insulin pulses was greater in the Px group (P < 0.001) while the amplitude of the C-peptide pulses did not differ between the groups. Cross-correlation analysis demonstrated maximal correlation coefficients at a lag of 0 min between insulin and C-peptide (control r = 0.33, P < 0.0001; Kx r = 0.17, P = 0.06) and between insulin and glucose (control r = 0.21, P < 0.001; Kx r = 0.20, P < 0.02) in the control and Kx groups, respectively, whereas no significant correlations were observed at any lag in the Px group. Thus, insulin oscillations, which are of larger amplitude and occur with greater frequency than in normal control subjects, may be detected in the peripheral circulation after pancreas transplant. Although their persistence after transplant supports the hypothesis that they reflect the existence of an intrinsic islet cell pacemaker, the increased frequency of the oscillations in the Px group raises the possibility that this intrinsic pacemaker in normal subjects may be modified by extrinsic neural factors.