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

2018 Fiscal Year Annual Research Report

• Project/Area Number: 16F16418
• Research Institution: Kobe University
• Principal Investigator: 清野 進 神戸大学, 医学研究科, 特命教授 (80236067)
• Co-Investigator(Kenkyū-buntansha): CARMEAN CHRISTOPHER 神戸大学, 医学研究科, 外国人特別研究員
• Project Period (FY): 2016-10-07 – 2019-03-31
• Keywords: arcenic / diabetes / insulin secretion / serotonin / glucuronidation / toxicology / serotonin

Outline of Annual Research Achievements

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.

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] イリノイ大学シカゴ校(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: イリノイ大学シカゴ校
• [Journal Article] Arsenic modifies serotonin metabolism through glucuronidation in pancreatic beta-cells (2019)
  • Author(s): Carmean CM, Yokoi N, Takahashi H, Oduori OS, Kang C, Kanagawa A, Kirkley AG, Han G, Landeche M, Hidaka S, Katoh M, Sargis RM, Seino S
  • Journal Title: American Journal of Physiology Endocrinology and Metabolism Volume: 316 Pages: 464/474
  • DOI: 10.1152/ajpendo00302.2018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Braving the element: pancreatic beta-cell dysfunction and adaptation in response to inorganic arsenic exposure (invited review) (2019)
  • Author(s): Carmean CM and Seino S
  • Journal Title: Frontiers in Endocrinology Volume: 印刷中 Pages: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Arsenic modifies serotonin metabolism through glucuronidation in pancreatic beta-cells. (2018)
  • Author(s): Carmean CM, Yokoi N, Seino S, Sergis RM
  • Organizer: American Diabetes Association's 78th Scientific Sessions
  • Int'l Joint Research
• [Presentation] Knockdown of arsenic-induced genes recovers pancreatic beta-cells from arsenic-associated functional defects (2018)
  • Author(s): Carmean CM, Yokoi N, Takahashi H, Kanagawa A, Kang CJ, Sargis RM, Seino S
  • Organizer: The 61st Annual Meeting of the Japan Diabetes Society