Sustained NF-κB Activation and Inhibition in β-Cells Have Minimal Effects on Function and Islet Transplant Outcomes

Aileen J F King, Yongjing Guo, Dongsheng Cai, Jennifer Hollister-Lock, Brooke Morris, Alison Salvatori, John A. Corbett, Susan Bonner-Weir, Steven E. Shoelson, Gordon C. Weir

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The activation of the transcription factor NF-κB leads to changes in expression of many genes in pancreatic β-cells. However, the role of NF-κB activation in islet transplantation has not been fully elucidated. The aim of the present study was to investigate whether the state of NF-κB activation would influence the outcome of islet transplantation. Transgenic mice expressing a dominant active IKKβ (constitutively active) or a non-degradable form of IκBα (constitutive inhibition) under control of the rat insulin promoter were generated. Islets from these mice were transplanted into streptozotocin diabetic mice in suboptimal numbers. Further, the effects of salicylate (an inhibitor of NF-κB) treatment of normal islets prior to transplantation, and the effects of salicylate administration to mice prior to and after islet implantation were evaluated. Transplantation outcomes were not affected using islets expressing a non-degradable form of IκBα when compared to wild type controls. However, the transplantation outcomes using islets isolated from mice expressing a constitutively active mutant of NF-κB were marginally worse, although no aberrations of islet function in vitro could be detected. Salicylate treatment of normal islets or mice had no effect on transplantation outcome. The current study draws attention to the complexities of NF-κB in pancreatic beta cells by suggesting that they can adapt with normal or near normal function to both chronic activation and inhibition of this important transcription factor.

Original languageEnglish (US)
Article numbere77452
JournalPLoS One
Volume8
Issue number10
DOIs
StatePublished - Oct 18 2013
Externally publishedYes

Fingerprint

Transplants
Salicylates
Chemical activation
salicylates
Transplantation
mice
Islets of Langerhans Transplantation
Transcription Factors
cells
Streptozocin
transcription factors
Aberrations
Insulin-Secreting Cells
Rats
Genes
streptozotocin
islets of Langerhans
Transgenic Mice
Insulin
insulin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sustained NF-κB Activation and Inhibition in β-Cells Have Minimal Effects on Function and Islet Transplant Outcomes. / King, Aileen J F; Guo, Yongjing; Cai, Dongsheng; Hollister-Lock, Jennifer; Morris, Brooke; Salvatori, Alison; Corbett, John A.; Bonner-Weir, Susan; Shoelson, Steven E.; Weir, Gordon C.

In: PLoS One, Vol. 8, No. 10, e77452, 18.10.2013.

Research output: Contribution to journalArticle

King, AJF, Guo, Y, Cai, D, Hollister-Lock, J, Morris, B, Salvatori, A, Corbett, JA, Bonner-Weir, S, Shoelson, SE & Weir, GC 2013, 'Sustained NF-κB Activation and Inhibition in β-Cells Have Minimal Effects on Function and Islet Transplant Outcomes', PLoS One, vol. 8, no. 10, e77452. https://doi.org/10.1371/journal.pone.0077452
King, Aileen J F ; Guo, Yongjing ; Cai, Dongsheng ; Hollister-Lock, Jennifer ; Morris, Brooke ; Salvatori, Alison ; Corbett, John A. ; Bonner-Weir, Susan ; Shoelson, Steven E. ; Weir, Gordon C. / Sustained NF-κB Activation and Inhibition in β-Cells Have Minimal Effects on Function and Islet Transplant Outcomes. In: PLoS One. 2013 ; Vol. 8, No. 10.
@article{0348a85bca5d48e2bde6b4b2f3507f8f,
title = "Sustained NF-κB Activation and Inhibition in β-Cells Have Minimal Effects on Function and Islet Transplant Outcomes",
abstract = "The activation of the transcription factor NF-κB leads to changes in expression of many genes in pancreatic β-cells. However, the role of NF-κB activation in islet transplantation has not been fully elucidated. The aim of the present study was to investigate whether the state of NF-κB activation would influence the outcome of islet transplantation. Transgenic mice expressing a dominant active IKKβ (constitutively active) or a non-degradable form of IκBα (constitutive inhibition) under control of the rat insulin promoter were generated. Islets from these mice were transplanted into streptozotocin diabetic mice in suboptimal numbers. Further, the effects of salicylate (an inhibitor of NF-κB) treatment of normal islets prior to transplantation, and the effects of salicylate administration to mice prior to and after islet implantation were evaluated. Transplantation outcomes were not affected using islets expressing a non-degradable form of IκBα when compared to wild type controls. However, the transplantation outcomes using islets isolated from mice expressing a constitutively active mutant of NF-κB were marginally worse, although no aberrations of islet function in vitro could be detected. Salicylate treatment of normal islets or mice had no effect on transplantation outcome. The current study draws attention to the complexities of NF-κB in pancreatic beta cells by suggesting that they can adapt with normal or near normal function to both chronic activation and inhibition of this important transcription factor.",
author = "King, {Aileen J F} and Yongjing Guo and Dongsheng Cai and Jennifer Hollister-Lock and Brooke Morris and Alison Salvatori and Corbett, {John A.} and Susan Bonner-Weir and Shoelson, {Steven E.} and Weir, {Gordon C.}",
year = "2013",
month = "10",
day = "18",
doi = "10.1371/journal.pone.0077452",
language = "English (US)",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

TY - JOUR

T1 - Sustained NF-κB Activation and Inhibition in β-Cells Have Minimal Effects on Function and Islet Transplant Outcomes

AU - King, Aileen J F

AU - Guo, Yongjing

AU - Cai, Dongsheng

AU - Hollister-Lock, Jennifer

AU - Morris, Brooke

AU - Salvatori, Alison

AU - Corbett, John A.

AU - Bonner-Weir, Susan

AU - Shoelson, Steven E.

AU - Weir, Gordon C.

PY - 2013/10/18

Y1 - 2013/10/18

N2 - The activation of the transcription factor NF-κB leads to changes in expression of many genes in pancreatic β-cells. However, the role of NF-κB activation in islet transplantation has not been fully elucidated. The aim of the present study was to investigate whether the state of NF-κB activation would influence the outcome of islet transplantation. Transgenic mice expressing a dominant active IKKβ (constitutively active) or a non-degradable form of IκBα (constitutive inhibition) under control of the rat insulin promoter were generated. Islets from these mice were transplanted into streptozotocin diabetic mice in suboptimal numbers. Further, the effects of salicylate (an inhibitor of NF-κB) treatment of normal islets prior to transplantation, and the effects of salicylate administration to mice prior to and after islet implantation were evaluated. Transplantation outcomes were not affected using islets expressing a non-degradable form of IκBα when compared to wild type controls. However, the transplantation outcomes using islets isolated from mice expressing a constitutively active mutant of NF-κB were marginally worse, although no aberrations of islet function in vitro could be detected. Salicylate treatment of normal islets or mice had no effect on transplantation outcome. The current study draws attention to the complexities of NF-κB in pancreatic beta cells by suggesting that they can adapt with normal or near normal function to both chronic activation and inhibition of this important transcription factor.

AB - The activation of the transcription factor NF-κB leads to changes in expression of many genes in pancreatic β-cells. However, the role of NF-κB activation in islet transplantation has not been fully elucidated. The aim of the present study was to investigate whether the state of NF-κB activation would influence the outcome of islet transplantation. Transgenic mice expressing a dominant active IKKβ (constitutively active) or a non-degradable form of IκBα (constitutive inhibition) under control of the rat insulin promoter were generated. Islets from these mice were transplanted into streptozotocin diabetic mice in suboptimal numbers. Further, the effects of salicylate (an inhibitor of NF-κB) treatment of normal islets prior to transplantation, and the effects of salicylate administration to mice prior to and after islet implantation were evaluated. Transplantation outcomes were not affected using islets expressing a non-degradable form of IκBα when compared to wild type controls. However, the transplantation outcomes using islets isolated from mice expressing a constitutively active mutant of NF-κB were marginally worse, although no aberrations of islet function in vitro could be detected. Salicylate treatment of normal islets or mice had no effect on transplantation outcome. The current study draws attention to the complexities of NF-κB in pancreatic beta cells by suggesting that they can adapt with normal or near normal function to both chronic activation and inhibition of this important transcription factor.

UR - http://www.scopus.com/inward/record.url?scp=84885725858&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885725858&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0077452

DO - 10.1371/journal.pone.0077452

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

M1 - e77452

ER -