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例)研究発表 生命科学科

セミナー第141回 臨床化学セミナー【Larry L. Hillblom Islet Research Center Dr Slavica Tudzarova】

  • [開催日時]2018年4月19日(木)16:00-17:00
  • [開催場所]北棟2階 検査部会議室
  • [対象]九州大学・九大病院の教職員、研究員、学生
第141回 臨床化学セミナーを下記のように予定しております。
セミナーは英語で行われます/ The speaker will give us a lecture in English.

HIF1α-PFKFB3 tissue/injury repair program mediates β-cell dysfunction in diabetes – implications for mitochondrial form and function

Dr Slavica Tudzarova, Assistant Professor and Principal Investigator
Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, UCLA (USA)

日時:2018年4月19日(木曜日) 16:00~17:00
会場:九州大学病院 北棟2階 検査部会議室

A wide range of changes have been described in β-cells in type-2-diabetes (T2D) including islet amyloid pancreatic polypeptide (IAPP) misfolding. Our data support the novel concept that the abnormalities detected in β-cells in T2D are adaptive manifestations of a stalled tissue injury/repair program mediated by HIF1α-PFKFB3 network. HIF1α-PFKFB3 network is highly activated in β-cells in humans with T2D and reproduced in both human and rodent cell lines and human IAPP transgenic rodent models.
Our results reveal that first, upon injury HIF1α-PFKFB3 stress pathway induced a protective metabolic remodeling with a marked increase in flux through glycolysis that is disengaged from the TCA cycle to generate ATP independent of oxygen availability and substrates for DNA repair synthesis. Glycolysis enabled the mitochondrial network to adopt the fragmented posture that protects mitochondria from deleterious Ca2+ toxicity. The next stage of the adaptive response permits cells to re-enter cell cycle and repopulate the affected tissue. When the injury is sustained and the tissue does not have the capacity for replication/regeneration as in the case of β-cells in adults, the cells become trapped midpoint in the injury/repair program. The HIF1α-PFKFB3 stress/repair pathway, therefore, constrains the rate of cell loss at the expense of β-cell dysfunction.

世話人:安川 武宏(臨床検査医学分野、内線5752)