TY - JOUR
T1 - Coordinate pulsatile insulin secretion by chronic intraportally transplanted islets in the isolated perfused rat liver
AU - Pørksen, Niels
AU - Munn, Stephen
AU - Ferguson, Deanna
AU - O'Brien, Timothy
AU - Veldhuis, Johannes
AU - Butler, Peter
PY - 1994/7
Y1 - 1994/7
N2 - 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.
AB - 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.
KW - diabetes mellitus
KW - insulin
KW - islet innervation
KW - islet transplantation
KW - pulsatility
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U2 - 10.1172/JCI117310
DO - 10.1172/JCI117310
M3 - Article
C2 - 8040264
AN - SCOPUS:0028338938
SN - 0021-9738
VL - 94
SP - 219
EP - 227
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 1
ER -