Duodenal GLP-1 signaling regulates hepatic glucose production through a PKC-δ-dependent neurocircuitry.
Duodenal GLP-1 signaling regulates hepatic glucose production through a PKC-δ-dependent neurocircuitry.
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十二指肠 GLP-1 信号通过 PKC-δ 依赖性神经回路调节肝葡萄糖产生
DOI：
10.1038/cddis.2017.28
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发表时间：
2017-02-09
影响因子：
9
通讯作者：
Yang G
中科院分区：
文献类型：
--
作者：
Yang M;Wang J;Wu S;Yuan L;Zhao X;Liu C;Xie J;Jia Y;Lai Y;Zhao AZ;Boden G;Li L;Yang G
肠胰高血糖素样肽-1 （GLP-1）是一种刺激胰岛素分泌并作为神经肽控制葡萄糖稳态的激素，但肠胰高血糖素样肽-1是否对肝脏葡萄糖生成（HGP）有控制作用尚不清楚。本研究发现，大鼠十二指肠内灌注GLP-1可激活十二指肠PKC-δ，降低HGP，并伴有肝脏糖异生酶表达减少和肝脏胰岛素信号传导增加。然而，将GLP-1受体拮抗剂Ex-9或PKC-δ抑制剂rottlerin与GLP-1共同输注肠道，会使GLP-1在钳夹期间降低HGP和增加肝脏胰岛素信号的能力丧失。大鼠十二指肠GLP-1的代谢和分子信号效应也通过与丁卡因共输注、对背脊髓复合体内n -甲基-d-天冬氨酸受体的药理抑制或肝迷走神经切断术被否定。总之，我们确定了肠道GLP-1信号的神经糖调节功能。
Intestinal glucagon-like peptide-1 (GLP-1) is a hormone that stimulates insulin secretion and acts as a neuropeptide to control glucose homeostasis, but little is known whether intestinal GLP-1 has any effect in the control of hepatic glucose production (HGP). Here we found that intraduodenal infusion of GLP-1 activated duodenal PKC-δ, lowered HGP and was accompanied by a decrease in hepatic expression of gluconeogenic enzymes and an increase in hepatic insulin signaling in rats. However, gut co-infusion of either the GLP-1 receptor antagonist Ex-9, or the PKC-δ inhibitor rottlerin with GLP-1, negated the ability of gut GLP-1 to lower HGP and to increase hepatic insulin signaling during clamps. The metabolic and molecular signal effects of duodenal GLP-1 were also negated by co-infusion with tetracaine, pharmacologic inhibition of N-methyl-d-aspartate receptors within the dorsalvagal complex, or hepatic vagotomy in rats. In summary, we identified a neural glucoregulatory function of gut GLP-1 signaling.