Murine remote preconditioning increases glucose uptake and suppresses gluconeogenesis in hepatocytes via a brain-liver neurocircuit, leading to counteracting glucose intolerance

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08427
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kochi University
• Principal Investigator: Kurabayashi Atsushi 高知大学, 教育研究部医療学系連携医学部門, 准教授 (40346713)
• Co-Investigator(Kenkyū-buntansha): 柿沼 由彦 日本医科大学, 大学院医学研究科, 大学院教授 (40233944) ; 井上 啓史 高知大学, 教育研究部医療学系臨床医学部門, 教授 (00294827)
• Co-Investigator(Renkei-kenkyūsha): FURIHATA MUTSUO 高知大学, 教育研究部医療学系連携医学部門, 教授 (10209158)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 虚血再灌流モデル / 糖取り込み / 糖新生 / 副交感神経 / 迷走神経

Outline of Final Research Achievements

Our previous study revealed that hindlimb ischaemia-reperfusion (IR) activates cardiac acetylcholine (ACh) synthesis through the cholinergic nervous system and cell-derived ACh accelerates glucose uptake. However, the mechanisms regulating glucose metabolism in vivo remain unknown. Using C57BL/6J mice, the effects of IR on blood sugar (BS), glucose uptake, central parasympathetic nervous system (PNS) activity and hepatic gluconeogenic enzyme activities were assessed. IR decreased BS levels and leaded to neuronal activation of the center of the PNS. IR specifically downregulated hepatic gluconeogenic enzyme expression and activities and accelerated hepatic glucose uptake. Moreover, IR significantly attenuated hyperglycaemia in murine model of type I and II diabetes mellitus. IR provides another insight into a therapeutic modality for diabetes mellitus due to regulating gluconeogenesis and glucose-uptake and advocates an adjunctive mode rectifying disturbed glucose metabolism.

Free Research Field

病理学