Yang Mengliu, Wang Jinzhi, Wu Shaobo, Yuan Lei, Zhao Xiaodong, Liu Chaohong, Xie Jing, Jia Yanjun, Lai Yerui, Zhao Allan Zijian, Boden Guenther, Li Ling, Yang Gangyi
Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Chongqing Key Lab of Child Infection and Immunity Children's Hospital of Chongqing Medical University, Chongqing, China.
Cell Death Dis. 2017 Feb 9;8(2):e2609. doi: 10.1038/cddis.2017.28.
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.
肠胰高血糖素样肽-1（GLP-1）是一种刺激胰岛素分泌的激素，并作为一种神经肽来控制葡萄糖稳态，但肠道GLP-1在控制肝糖生成（HGP）方面是否有任何作用却知之甚少。在这里，我们发现十二指肠内注入GLP-1可激活十二指肠蛋白激酶C-δ（PKC-δ），降低HGP，并伴随着大鼠肝脏糖异生酶表达的减少和肝脏胰岛素信号传导的增加。然而，在钳夹期间，将GLP-1受体拮抗剂Ex-9或PKC-δ抑制剂罗特lerin与GLP-1共同注入肠道，会消除肠道GLP-1降低HGP和增加肝脏胰岛素信号传导的能力。十二指肠GLP-1的代谢和分子信号作用也会因与丁卡因共同注入、对背迷走神经复合体中N-甲基-D-天冬氨酸受体的药理抑制或大鼠肝迷走神经切断术而被消除。总之，我们确定了肠道GLP-1信号传导的神经糖调节功能。
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