Institut National de la Santé et de la Recherche Médicale, U1048, Toulouse, France.
PLoS One. 2011;6(6):e21184. doi: 10.1371/journal.pone.0021184. Epub 2011 Jun 16.
Daily variations in lipid concentrations in both gut lumen and blood are detected by specific sensors located in the gastrointestinal tract and in specialized central areas. Deregulation of the lipid sensors could be partly involved in the dysfunction of glucose homeostasis. The study aimed at comparing the effect of Medialipid (ML) overload on insulin secretion and sensitivity when administered either through the intestine or the carotid artery in mice.
METHODOLOGY/PRINCIPAL FINDINGS: An indwelling intragastric or intracarotid catheter was installed in mice and ML or an isocaloric solution was infused over 24 hours. Glucose and insulin tolerance and vagus nerve activity were assessed. Some mice were treated daily for one week with the anti-lipid peroxidation agent aminoguanidine prior to the infusions and tests. The intestinal but not the intracarotid infusion of ML led to glucose and insulin intolerance when compared with controls. The intestinal ML overload induced lipid accumulation and increased lipid peroxidation as assessed by increased malondialdehyde production within both jejunum and duodenum. These effects were associated with the concomitant deregulation of vagus nerve. Administration of aminoguanidine protected against the effects of lipid overload and normalized glucose homeostasis and vagus nerve activity.
CONCLUSIONS/SIGNIFICANCE: Lipid overload within the intestine led to deregulation of gastrointestinal lipid sensing that in turn impaired glucose homeostasis through changes in autonomic nervous system activity.
位于胃肠道和专门的中枢区域的特定传感器可以检测到肠道腔和血液中脂质浓度的日常变化。脂质传感器的失调可能部分涉及葡萄糖稳态的功能障碍。本研究旨在比较肠内或颈动脉内给予 Medialipid（ML）过载对小鼠胰岛素分泌和敏感性的影响。
方法/主要发现：在小鼠中安装了一个留置胃内或颅内导管，并在 24 小时内输注 ML 或等热量溶液。评估葡萄糖和胰岛素耐量以及迷走神经活动。一些小鼠在输注和测试前一周每天用抗脂质过氧化剂氨基胍治疗。与对照组相比，肠内而不是颅内输注 ML 导致葡萄糖和胰岛素不耐受。肠道 ML 过载导致脂质积累和脂质过氧化增加，如空肠和十二指肠中丙二醛产量增加所评估的那样。这些影响与迷走神经的同时失调有关。氨基胍的给药可预防脂质过载的影响，并使葡萄糖稳态和迷走神经活动正常化。
结论/意义：肠道内的脂质过载导致胃肠道脂质感知失调，进而通过自主神经系统活动的变化损害葡萄糖稳态。
