In vivo studies of beta-cell secretory function have demonstrated the
existence of rapid insulin oscillations of small amplitude recurring e
very 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 a
t 2-min intervals for 90 min from six successful Px patients with type
I diabetes mellitus, from six normal nondiabetic control subjects, an
d from three Kx subjects. A computerized algorithm (ULTRA) was used fo
r pulse detection. In the Px group, the average insulin pulse period w
as 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. Spectra
l analysis confirmed that the frequency of the insulin pulses was incr
eased in the Px group. The absolute amplitude of the insulin pulses wa
s greater in the Px group (P < 0.001) while the amplitude of the C-pep
tide pulses did not differ between the groups. Cross-correlation analy
sis demonstrated maximal correlation coefficients at a lag of 0 min be
tween 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 < 0.0
01; 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 P
x 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. Alth
ough their persistence after transplant supports the hypothesis that t
hey reflect the existence of an intrinsic islet cell pacemaker, the in
creased frequency of the oscillations in the Px group raises the possi
bility that this intrinsic pacemaker in normal subjects may be modifie
d by extrinsic neural factors.