Murine remote preconditioning increases glucose uptake and suppresses gluconeogenesis in hepatocytes via a brain-liver neurocircuit, leading to counteracting glucose intolerance
Murine remote preconditioning increases glucose uptake and suppresses gluconeogenesis in hepatocytes via a brain-liver neurocircuit, leading to counteracting glucose intolerance
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DOI：
10.1016/j.diabres.2018.03.009
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发表时间：
2018-05-01
影响因子：
5.1
通讯作者：
Kakinuma, Yoshihiko
中科院分区：
文献类型：
--
作者：
Kurabayashi, Atsushi;Tanaka, Chiharu;Kakinuma, Yoshihiko
目的：我们以前的研究表明，周期性后肢缺血再灌注（IR）激活心脏乙酰胆碱（ACh）的合成通过胆碱能神经系统和细胞来源的ACh加速葡萄糖的摄取。然而，调节体内葡萄糖代谢的机制仍然未知。方法：采用雄性C57 BL/6 J小鼠，观察IR对血糖（BS）、葡萄糖摄取、中枢副交感神经系统（PNS）活性、肝脏促凋亡酶表达及ACh对肝细胞葡萄糖摄取的影响。IR使BS水平降低20%，并增加PNS中心（孤束和迷走神经背侧运动核）的c-fos免疫反应。IR特异性下调肝脏促凋亡酶（葡萄糖-6-磷酸酶和磷酸烯醇丙酮酸羧激酶）的表达和活性，并加速肝脏葡萄糖摄取。肝迷走神经分支的横断降低了这种摄取，并逆转了BS的降低。抑制hepaeogenic酶的表达逆转脑室内给药的胆碱乙酰转移酶抑制剂。此外，IR显着衰减高血糖症在小鼠模型中的I型和II型diabetesmellitus.Conclusions：IR提供了另一个洞察到糖尿病的治疗方式，由于调节血管生成和葡萄糖摄取，并主张一个积极的模式纠正紊乱的糖代谢。(C)2018爱思唯尔B. V.保留所有权利。
Aims: Our previous study revealed that cyclic 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. We investigated the effects and mechanisms of IR in mice under pathophysiological conditions.Methods: Using IR-subjected male C57BL/6J mice, the effects of IR on blood sugar (BS), glucose uptake, central parasympathetic nervous system (PNS) activity, hepatic gluconeogenic enzyme expression and those of ACh on hepatocellular glucose uptake were assessed.Results: IR decreased BS levels by 20% and increased c-fos immunoreactivity in the center of the PNS (the solitary tract and the dorsal motor vagal nucleus). IR specifically downregulated hepatic gluconeogenic enzyme expression and activities (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase) and accelerated hepatic glucose uptake. Transection of a hepatic vagus nerve branch decreased this uptake and reversed BS decrease. Suppressed gluconeogenic enzyme expression was reversed by intra-cerebroventricular administration of a choline acetyltransferase inhibitor. Moreover, IR significantly attenuated hyperglycaemia in murine model of type I and II diabetes mellitus.Conclusions: 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. (C) 2018 Elsevier B.V. All rights reserved.