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IL-1ß reciprocally regulates chemokine and insulin secretion in pancreatic
ß-cells via NF-?B.
Authors Burke SJ, Stadler K, Lu D, Gleason E, Han A, Donohoe DR, Rogers RC, Hermann GE,
Karlstad MD, Collier JJ
Submitted By Krisztian Stadler on 2/1/2016
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2015
Date Published 10/1/2015
Volume : Pages 309 : E715 - 26
PubMed Reference
Abstract Proinflammatory cytokines impact islet ß-cell mass and function by altering the
transcriptional activity within pancreatic ß-cells, producing increases in
intracellular nitric oxide abundance and the synthesis and secretion of
immunomodulatory proteins such as chemokines. Herein, we report that IL-1ß, a
major mediator of inflammatory responses associated with diabetes development,
coordinately and reciprocally regulates chemokine and insulin secretion. We
discovered that NF-?B controls the increase in chemokine transcription and
secretion as well as the decrease in both insulin secretion and proliferation in
response to IL-1ß. Nitric oxide production, which is markedly elevated in
pancreatic ß-cells exposed to IL-1ß, is a negative regulator of both
glucose-stimulated insulin secretion and glucose-induced increases in
intracellular calcium levels. By contrast, the IL-1ß-mediated production of the
chemokines CCL2 and CCL20 was not influenced by either nitric oxide levels or
glucose concentration. Instead, the synthesis and secretion of CCL2 and CCL20 in
response to IL-1ß were dependent on NF-?B transcriptional activity. We conclude
that IL-1ß-induced transcriptional reprogramming via NF-?B reciprocally
regulates chemokine and insulin secretion while also negatively regulating
ß-cell proliferation. These findings are consistent with NF-?B as a major
regulatory node controlling inflammation-associated alterations in islet ß-cell
function and mass.

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