Glucagon-like peptide-1 receptor is present in pancreatic acinar cells and regulates amylase secretion through cAMP
Glucagon-like peptide-1 receptor is present in pancreatic acinar cells and regulates amylase secretion through cAMP
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DOI：
10.1152/ajpgi.00293.2015
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发表时间：
2016-01-01
影响因子：
4.5
通讯作者：
Williams, John A.
中科院分区：
文献类型：
--
作者：
Hou, Yanan;Ernst, Stephen A.;Williams, John A.
胰高血糖素样肽-1（GLP-1）是一种葡萄糖肠降血糖素激素，可通过其受体（GLP-1 R）作用于胰腺β细胞并增加胰岛素分泌和产生。GLP-1 R激动剂在临床上用于治疗2型糖尿病。GLP-1还可在多个水平调节胰腺外分泌，包括通过中枢神经系统抑制、通过胰岛素间接刺激和直接刺激腺泡细胞。然而，尚不清楚GLP-1 R是否存在于胰腺腺泡中以及这些受体调节何种生理功能。在当前研究中，我们使用GLP-1 R敲除（KO）小鼠研究GLP-1 R在腺泡细胞中的作用。在急性分离的胰腺腺泡中检测到GLP-1 R的RNA表达。腺泡细胞形态和消化酶表达不受GLP-1 R缺失的影响。GLP-1诱导野生型（WT）腺泡中的淀粉酶分泌。在GLP-1 R KO小鼠中，这种作用被消除，而KO腺泡中血管活性肠肽诱导的淀粉酶释放显示出与WT腺泡相似的模式。GLP-1刺激WT腺泡中cAMP产生并增加蛋白激酶A介导的蛋白磷酸化，而KO腺泡中不存在这些作用。这些数据表明GLP-1 R存在于胰腺腺泡细胞中，GLP-1可通过其受体和cAMP信号通路调节分泌。
Glucagon-like peptide-1 (GLP-1) is a glucoincretin hormone that can act through its receptor (GLP-1R) on pancreatic beta-cells and increase insulin secretion and production. GLP-1R agonists are used clinically to treat type 2 diabetes. GLP-1 may also regulate the exocrine pancreas at multiple levels, including inhibition through the central nervous system, stimulation indirectly through insulin, and stimulation directly on acinar cells. However, it has been unclear whether GLP-1R is present in pancreatic acini and what physiological functions these receptors regulate. In the current study we utilized GLP-1R knockout (KO) mice to study the role of GLP-1R in acinar cells. RNA expression of GLP-1R was detected in acutely isolated pancreatic acini. Acinar cell morphology and expression of digestive enzymes were not affected by loss of GLP-1R. GLP-1 induced amylase secretion in wild-type (WT) acini. In GLP-1R KO mice, this effect was abolished, whereas vasoactive intestinal peptide-induced amylase release in KO acini showed a pattern similar to that in WT acini. GLP-1 stimulated cAMP production and increased protein kinase A-mediated protein phosphorylation in WT acini, and these effects were absent in KO acini. These data show that GLP-1R is present in pancreatic acinar cells and that GLP-1 can regulate secretion through its receptor and cAMP signaling pathway.