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七氟醚损害体内胰岛素分泌和组织特异性葡萄糖摄取功能

 罂粟花anesthGH 2021-07-21

  

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Sevoflurane Impairs Insulin Secretion and Tissue-Specific Glucose Uptake In Vivo

    摘 要     

1
背景与目的
3
结果
2
方法
4
结论

背景及目的:麻醉药物可严重的影响底物代谢。这给临床患者和糖尿病的动物研究带来了挑战。七氟醚可以在几个步骤影响葡萄糖体内平衡的调节,但组织特异性反应仍有待确定。该研究的目的是探究七氟醚麻醉对高胰岛素钳制条件下葡萄糖稳态的药理作用,这是评估全身胰岛素敏感性的金标准方法。

1

方法:有意识的小鼠(n = 6)和七氟醚麻醉的小鼠(n = 8)进行高胰岛素血症钳制,其中在葡萄糖输注期间持续输注胰岛素和供体血液以维持异常血糖。注入2- [1-1C] - 脱氧-D-葡萄糖以确定脂肪组织、心脏、脑和骨骼肌中葡萄糖的组织特异性摄取。

结果:七氟醚麻醉严重损害胰岛素刺激的全身葡萄糖摄取,表现为葡萄糖输注率(GIR)降低50%。与有意识的小鼠相比,与七氟醚麻醉小鼠的脑、比目鱼肌、肱三头肌和腓肠肌中的葡萄糖摄取减少有关。在七氟醚麻醉期间,血浆游离脂肪酸(FFA)增加了42%,这是一种有效的胰岛素抵抗诱导剂。此外,在禁食、麻醉的小鼠中胰岛β细胞的胰岛素分泌较低。

结论:七氟醚麻醉损害胰岛素分泌,诱导小鼠胰岛素抵抗并降低非胰岛素敏感组织(如大脑)的葡萄糖摄取。其潜在的机制可能与七氟醚诱导血浆游离脂肪酸(FFA)活化有关。

    原始文献来源   

Høyer KF, Nielsen TS, Risis S, Treebak JT, Jessen N. Sevoflurane Impairs Insulin Secretion and Tissue-Specific Glucose Uptake In Vivo.Basic Clin Pharmacol Toxicol. 2018 Jun 28. doi: 10.1111/bcpt.13087. 

Abstract

The use of anaesthetics severely influences substrate metabolism. This poses challenges for patients in clinical settings and for the use of animals in diabetes research. Sevoflurane can affect regulation of glucose homeostasis at several steps, but the tissue-specific response remains to be determined. The aim of the study was to investigate the pharmacological effect of sevoflurane anaesthesia on glucose homeostasis during hyperinsulinaemic clamp conditions, the gold standard method for assessment of whole-body insulin sensitivity. Conscious mice (n=6) and mice under sevoflurane anaesthesia (n=8) underwent a hyperinsulinaemic clamp where constant infusion of insulin and donor blood was administered during variable glucose infusion to maintain isoglycaemia. 2-[1-14 C]-deoxy-D-glucose was infused to determine tissue-specific uptake of glucose in adipose tissue, heart, brain and skeletal muscle. Sevoflurane anaesthesia severely impaired insulin-stimulated whole-body glucose uptake demonstrated by a 50% lower glucose infusion rate (GIR). This was associated with decreased glucose uptake in brain, soleus, triceps and gastrocnemius muscles in sevoflurane-anaesthetized mice compared to conscious mice. Plasma Free Fatty Acids (FFA), a potent inducer of insulin resistance, increased by 42% in mice during sevoflurane anaesthesia. In addition, insulin secretion from pancreatic β-cell was lower in fasted, anaesthetized mice. Sevoflurane anaesthesia impairs insulin secretion, induces insulin resistance in mice and reduces glucose uptake in non-insulin sensitive tissue like the brain. The underlying mechanisms may involve sevoflurane-induced mobilization of FFA. This article is protected by copyright. All rights reserved.


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