Mechanism of rapid-phase insulin response to elevation of portal glucose concentration

Mechanism of rapid-phase insulin response to elevation of portal glucose concentration
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DOI:
10.1152/ajpendo.00536.2006
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发表时间:
2007-08-01
影响因子:
5.1
通讯作者:
Takeda, Eiji
Takeda, Eiji
中科院分区:
医学2区
文献类型:
--
作者:
Fukaya, Makiko;Mizuno, Akira;Takeda, Eiji

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肝门区对血糖感应很重要;然而,肝门区血糖感应系统与餐后胰岛素反应快速时相之间的关系尚不清楚。我们检测了清醒大鼠门脉内低剂量葡萄糖输注是否会产生快速时相胰岛素反应,并与颈静脉内葡萄糖输注反应进行比较,并评估这种感觉系统是否与自主神经活动有关。两次输液3min时血糖浓度的升高没有差别,但仅在门脉内输液中检测到快速时相胰岛素反应。门静脉注射少量葡萄糖后3min,胰岛素反应迅速,而颈静脉注射后胰岛素反应不明显。此外,这种胰岛素反应也是由门静脉注射果糖引起的,但不是由非代谢糖引起的。肝迷走神经切断组和6-羟基多巴胺化学交感神经切断组大鼠在门静脉输注3min时的快相胰岛素反应与对照组相比无明显差异,而阿托品化学迷走神经切断组大鼠的快相胰岛素反应消失。我们的结论是,肝门区葡萄糖浓度的升高诱导了来自无法检测到的传感器的传入信号,这些信号刺激胰腺通过胆碱能神经作用诱导快速时相胰岛素反应。
The hepatoportal region is important for glucose sensing; however, the relationship between the hepatoportal glucose-sensing system and the postprandial rapid phase of the insulin response has been unclear. We examined whether a rapid-phase insulin response to low amounts of intraportal glucose infusion would occur, compared that with the response to intrajugular glucose infusion in conscious rats, and assessed whether this sensing system was associated with autonomic nerve activity. The increases in plasma glucose concentration did not differ between the two infusions at 3 min, but the rapid-phase insulin response was detected only in the intraportal infusion. A sharp and rapid insulin response was observed at 3 min after intraportal infusion of a small amount of glucose but not after intrajugular infusion. Furthermore, this insulin response was also induced by intraportal fructose infusion but not by nonmetabolizable sugars. The rapid-phase insulin response at 3 min during intraportal infusion did not differ between rats that had undergone hepatic vagotomy or chemical sympathectomy with 6-hydroxydopamine compared with control rats, but this response disappeared in rats that had undergone chemical vagotomy with atropine. We conclude that the elevation of glucose concentration in the hepatoportal region induced afferent signals from undetectable sensors and that these signals stimulate pancreas to induce the rapid-phase insulin response via cholinergic nerve action.