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

Niels Pørksen, Stephen Munn, Deanna Ferguson, Timothy O'Brien, Johannes D Veldhuis, Peter Butler

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)219-227
Number of pages9
JournalJournal of Clinical Investigation
Volume94
Issue number1
StatePublished - Jul 1994
Externally publishedYes

Fingerprint

Insulin
Liver
Transplantation
Synaptophysin
Pentobarbital
Streptozocin
Glucose

Keywords

  • diabetes mellitus
  • insulin
  • islet innervation
  • islet transplantation
  • pulsatility

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Pørksen, N., Munn, S., Ferguson, D., O'Brien, T., Veldhuis, J. D., & Butler, P. (1994). Coordinate pulsatile insulin secretion by chronic intraportally transplanted islets in the isolated perfused rat liver. Journal of Clinical Investigation, 94(1), 219-227.

Coordinate pulsatile insulin secretion by chronic intraportally transplanted islets in the isolated perfused rat liver. / Pørksen, Niels; Munn, Stephen; Ferguson, Deanna; O'Brien, Timothy; Veldhuis, Johannes D; Butler, Peter.

In: Journal of Clinical Investigation, Vol. 94, No. 1, 07.1994, p. 219-227.

Research output: Contribution to journalArticle

Pørksen, N, Munn, S, Ferguson, D, O'Brien, T, Veldhuis, JD & Butler, P 1994, 'Coordinate pulsatile insulin secretion by chronic intraportally transplanted islets in the isolated perfused rat liver', Journal of Clinical Investigation, vol. 94, no. 1, pp. 219-227.
Pørksen, Niels ; Munn, Stephen ; Ferguson, Deanna ; O'Brien, Timothy ; Veldhuis, Johannes D ; Butler, Peter. / Coordinate pulsatile insulin secretion by chronic intraportally transplanted islets in the isolated perfused rat liver. In: Journal of Clinical Investigation. 1994 ; Vol. 94, No. 1. pp. 219-227.
@article{9a0f1fbc5ebd45b1b55d65318a1ca5e9,
title = "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.",
keywords = "diabetes mellitus, insulin, islet innervation, islet transplantation, pulsatility",
author = "Niels P{\o}rksen and Stephen Munn and Deanna Ferguson and Timothy O'Brien and Veldhuis, {Johannes D} and Peter Butler",
year = "1994",
month = "7",
language = "English (US)",
volume = "94",
pages = "219--227",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "1",

}

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 D

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

UR - http://www.scopus.com/inward/record.url?scp=0028338938&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028338938&partnerID=8YFLogxK

M3 - Article

VL - 94

SP - 219

EP - 227

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 1

ER -