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 approximately 2 x 10(3) 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 micrograms/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 (approximately 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.
N Pørksen, S Munn, D Ferguson, T O'Brien, J Veldhuis, P Butler
The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.