ヒ素による糖代謝異常における膵α細胞の役割に関する研究

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Previously our RNA sequencing and metabolomics data identified the serotonin disposal pathway as a possible mediator of arsenic’s effects. We followed up on these results by measuring the gene expression of other serotonin metabolism-associated genes, and we measured the enzymatic rate of serotonin conjugation to glucuronic acid to form serotonin-glucuronide. Additionally, we developed a series of gene candidate knockouts. We evaluated their functional characteristics, including glucose-induced insulin secretion, serotonin levels, and serotonin glucuronidation enzymatic activity. We also confirmed that the same gene expression patterns observed in MIN6-K8 cells were also replicated in primary human islets. Both mouse and human islets up-regulated Ugt1a6a (mouse) or UGT1A6 (human) in response to arsenic exposure. A paper on these findings was published in a peer-reviewed journal.