| Project/Area Number |
15K20063
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Anesthesiology
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| Research Institution | Kyoto University (2016)
Kansai Medical University (2015) |
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Principal Investigator |
Suzuki Kengo 京都大学, 医学研究科, 助教 (90734658)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | HIF-1 / インスリン / セボフルラン / イソフルラン / セボフルレン / イソフルレン / 低酸素 / GSIS |
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| Outline of Final Research Achievements |
Several animal and human studies have indicated that volatile anesthetics impair glucose-stimulated insulin secretion (GSIS).
Isoflurane and sevoflurane inhibited GSIS significantly in a concentration-dependent manner. Oxygen consumption rate in MIN6 cells but to a lesser extent than the mitochondrial uncoupler, CCCP (5 μM). Isoflurane and sevoflurane significantly suppressed glucose-induced HIF-1alpha protein expression in MIN6 cells. HIF-1alpha protein expression, which was not affected by isoflurane. Inhibition of HIF-1 activity by YC-1 treatment and RNA interference-mediated knockdown of HIF-1alpha expression significantly suppressed GSIS in MIN6 cells.
Both the anesthetics inhibited the glucose-induced increase of ATP, which is dependent on intracellular hypoxia-induced HIF-1 activity, and suppressed GSIS at a clinically relevant dose in MIN6 cells.
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