Faculty Collaboration Database

Sustained NF-κB activation and inhibition in β-cells have minimal effects on function and islet transplant outcomes. PLoS One 2013;8(10):e77452

Date

11/10/2013

Pubmed ID

24204831

Pubmed Central ID

PMC3799630

DOI

10.1371/journal.pone.0077452

Scopus ID

2-s2.0-84885725858 (requires institutional sign-in at Scopus site)   10 Citations

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 List

King AJ, Guo Y, Cai D, Hollister-Lock J, Morris B, Salvatori A, Corbett JA, Bonner-Weir S, Shoelson SE, Weir GC

Author

John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Diabetes Mellitus, Experimental
Female
Gene Expression Regulation
I-kappa B Kinase
Insulin-Secreting Cells
Islets of Langerhans Transplantation
Male
Mice
Mice, Transgenic
NF-kappa B
Promoter Regions, Genetic
Rats
Salicylic Acid
Streptozocin
Treatment Outcome