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The HDAC Inhibitor Butyrate Impairs β Cell Function and Activates the Disallowed Gene Hexokinase I

Histone deacetylase (HDAC) inhibitors such as butyrate have been reported to reduce diabetes risk and protect insulin-secreting pancreatic β cells in animal models. However, studies on insulin-secreting cells in vitro have found that butyrate treatment resulted in impaired or inappropriate insulin s...

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Autores principales: Bridgeman, Stephanie, Ellison, Gaewyn, Newsholme, Philip, Mamotte, Cyril
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705743/
https://www.ncbi.nlm.nih.gov/pubmed/34948127
http://dx.doi.org/10.3390/ijms222413330
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author Bridgeman, Stephanie
Ellison, Gaewyn
Newsholme, Philip
Mamotte, Cyril
author_facet Bridgeman, Stephanie
Ellison, Gaewyn
Newsholme, Philip
Mamotte, Cyril
author_sort Bridgeman, Stephanie
collection PubMed
description Histone deacetylase (HDAC) inhibitors such as butyrate have been reported to reduce diabetes risk and protect insulin-secreting pancreatic β cells in animal models. However, studies on insulin-secreting cells in vitro have found that butyrate treatment resulted in impaired or inappropriate insulin secretion. Our study explores the effects of butyrate on insulin secretion by BRIN BD-11 rat pancreatic β cells and examined effects on the expression of genes implicated in β cell function. Robust HDAC inhibition with 5 mM butyrate or trichostatin A for 24 h in β cells decreased basal insulin secretion and content, as well as insulin secretion in response to acute stimulation. Treatment with butyrate also increased expression of the disallowed gene hexokinase I, possibly explaining the impairment to insulin secretion, and of TXNIP, which may increase oxidative stress and β cell apoptosis. In contrast to robust HDAC inhibition (>70% after 24 h), low-dose and acute high-dose treatment with butyrate enhanced nutrient-stimulated insulin secretion. In conclusion, although protective effects of HDAC inhibition have been observed in vivo, potent HDAC inhibition impairs β cell function in vitro. The chronic low dose and acute high dose butyrate treatments may be more reflective of in vivo effects.
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spelling pubmed-87057432021-12-25 The HDAC Inhibitor Butyrate Impairs β Cell Function and Activates the Disallowed Gene Hexokinase I Bridgeman, Stephanie Ellison, Gaewyn Newsholme, Philip Mamotte, Cyril Int J Mol Sci Article Histone deacetylase (HDAC) inhibitors such as butyrate have been reported to reduce diabetes risk and protect insulin-secreting pancreatic β cells in animal models. However, studies on insulin-secreting cells in vitro have found that butyrate treatment resulted in impaired or inappropriate insulin secretion. Our study explores the effects of butyrate on insulin secretion by BRIN BD-11 rat pancreatic β cells and examined effects on the expression of genes implicated in β cell function. Robust HDAC inhibition with 5 mM butyrate or trichostatin A for 24 h in β cells decreased basal insulin secretion and content, as well as insulin secretion in response to acute stimulation. Treatment with butyrate also increased expression of the disallowed gene hexokinase I, possibly explaining the impairment to insulin secretion, and of TXNIP, which may increase oxidative stress and β cell apoptosis. In contrast to robust HDAC inhibition (>70% after 24 h), low-dose and acute high-dose treatment with butyrate enhanced nutrient-stimulated insulin secretion. In conclusion, although protective effects of HDAC inhibition have been observed in vivo, potent HDAC inhibition impairs β cell function in vitro. The chronic low dose and acute high dose butyrate treatments may be more reflective of in vivo effects. MDPI 2021-12-11 /pmc/articles/PMC8705743/ /pubmed/34948127 http://dx.doi.org/10.3390/ijms222413330 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bridgeman, Stephanie
Ellison, Gaewyn
Newsholme, Philip
Mamotte, Cyril
The HDAC Inhibitor Butyrate Impairs β Cell Function and Activates the Disallowed Gene Hexokinase I
title The HDAC Inhibitor Butyrate Impairs β Cell Function and Activates the Disallowed Gene Hexokinase I
title_full The HDAC Inhibitor Butyrate Impairs β Cell Function and Activates the Disallowed Gene Hexokinase I
title_fullStr The HDAC Inhibitor Butyrate Impairs β Cell Function and Activates the Disallowed Gene Hexokinase I
title_full_unstemmed The HDAC Inhibitor Butyrate Impairs β Cell Function and Activates the Disallowed Gene Hexokinase I
title_short The HDAC Inhibitor Butyrate Impairs β Cell Function and Activates the Disallowed Gene Hexokinase I
title_sort hdac inhibitor butyrate impairs β cell function and activates the disallowed gene hexokinase i
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705743/
https://www.ncbi.nlm.nih.gov/pubmed/34948127
http://dx.doi.org/10.3390/ijms222413330
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