Coordinate pulsatile insulin secretion by chronic intraportally transplanted islets in the isolated perfused rat liver

Abstract

In the present studies we sought to address the following questions: do chronically transplanted intrahepatic islets (IHI-Tx) secrete insulin in a coordinate pulsatile manner, and, if so, is reestablishment of this coordinate pulsatility a function of time after transplantation? We studied isolated perfused livers at 10 mM glucose from 27 rats rendered diabetic with streptozotocin and then transplanted with ~ 2 x 103 islets, 2 (n = 5), 7 (n = 5), 30 (n = 5), and 200 (n = 12) d after transplantation. 12 out of 12 of the 200-d IHI-Tx secreted insulin in coordinate pulses (frequency 3.9±0.3 pulses/h, amplitude 15.2±2.4 nmol/min). In contrast, one out of five 2-d, zero out of five 7-d, and one out of five 30-d IHI-Tx showed pulsatile insulin secretion. Insulin secretion was markedly greater (76±13 vs 13±3 nmol/min, P < 0.0001) in the 200-d versus early IHI-Tx. Pentobarbital 25 μg/ml had no effect on total (13.9±3.9 vs 15.9±3.9 nmol/min), nonpulsatile (12.9±3.5 vs 14.1±3.3 nmol/min), or pulsatile (pulse amplitude 17.6±4.5 vs 20.0±4.2 nmol/min, pulse frequency 4.1±0.3 vs 4.0±0.7 pulses/h) insulin secretion. Using synaptophysin, islet innervation was documented in 12 out of 12 200-d IHI-Tx but in none of the early IHI-Tx. We conclude that established (~ 200 d) IHI-Tx secrete insulin in a coordinate pulsatile manner and that establishment of coordinate pulsatile insulin secretion by IHI-Tx is accompanied by increased total insulin secretion and is associated with islet reinnervation.