Cell Death and Disease (Jan 2022)

Sodium butyrate potentiates insulin secretion from rat islets at the expense of compromised expression of β cell identity genes

  • Shushu Wang,
  • Miaomiao Yuan,
  • Linlin Zhang,
  • Kecheng Zhu,
  • Chunxiang Sheng,
  • Feiye Zhou,
  • Zhaoqian Xu,
  • Qianqian Liu,
  • Yun Liu,
  • Jieli Lu,
  • Xiao Wang,
  • Libin Zhou

DOI
https://doi.org/10.1038/s41419-022-04517-1
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 10

Abstract

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Abstract Short-chain fatty acids (SCFAs) produced by the gut microbiota have been well demonstrated to improve metabolic homeostasis. However, the role of SCFAs in islet function remains controversial. In the present study, none of the sodium acetate, sodium propionate, and sodium butyrate (SB) displayed acute impacts on insulin secretion from rat islets, whereas long-term incubation of the three SCFAs significantly potentiated pancreatic β cell function. RNA sequencing (RNA-seq) revealed an unusual transcriptome change in SB-treated rat islets, with the downregulation of insulin secretion pathway and β cell identity genes, including Pdx1, MafA, NeuroD1, Gck, and Slc2a2. But these β cell identity genes were not governed by the pan-HDAC inhibitor trichostatin A. Overlapping analysis of H3K27Ac ChIP-seq and RNA-seq showed that the inhibitory effect of SB on the expression of multiple β cell identity genes was independent of H3K27Ac. SB treatment increased basal oxygen consumption rate (OCR), but attenuated glucose-stimulated OCR in rat islets, without altering the expressions of genes involved in glycolysis and tricarboxylic acid cycle. SB reduced the expression of Kcnj11 (encoding KATP channel) and elevated basal intracellular calcium concentration. On the other hand, SB elicited insulin gene expression in rat islets through increasing H3K18bu occupation in its promoter, without stimulating CREB phosphorylation. These findings indicate that SB potentiates islet function as a lipid molecule at the expense of compromised expression of islet β cell identity genes.