Brubaker P L
Department of Physiology, University of Toronto, Ontario, Canada.
Endocrinology. 1991 Jun;128(6):3175-82. doi: 10.1210/endo-128-6-3175.
The physiological regulation of intestinal proglucagon-derived peptide secretion has not been well studied. We have therefore used a fetal rat intestinal cell culture model to investigate the control of secretion of the gut glucagon-like immunoreactive (GLI) peptides by other intestinal regulatory peptides in vitro. Secretion of the intestinal GLI peptides was found to be stimulated in a dose-dependent fashion by the intestinal endocrine peptide, gastric inhibitory peptide (at greater than or equal to 10(-10) M, P less than 0.05), and by the neurocrine peptides, gastrin-releasing peptide (at greater than or equal to 10(-12) M, P less than 0.05), and calcitonin gene-related peptide (at greater than or equal to 10(-8) M, P less than 0.05). Gastrin-releasing peptide and its amphibian equivalent, bombesin were equipotent in stimulating GLI peptide secretion. In contrast, the endocrine and neurocrine intestinal somatostatin-related peptides, somatostatin-28 and -14, inhibited release of the GLI peptides, at concentrations of 10(-10) (P less than 0.01) and 10(-8) (P less than 0.01) M, respectively, with significant differences in potency between the two peptides detected at 10(-10) M (P less than 0.05). The inhibitory effects of both somatostatin-28 and -14 could be blocked by preincubation of the cells with pertussis toxin (P less than 0.05). Dose-dependent stimulation of gut GLI peptide secretion was also detected in response to treatment of cultured cells with sodium oleate (at 10(-4) M; P less than 0.05), or with the cholinergic agonist bethanecol (at greater than or equal to 100 microM; P less than 0.05). Other endocrine [cholecystokinin, glucagon, glucagon-like peptide-1(1-37), glucagon-like peptide-1(7-37), glucagon-like peptide-2, neurotensin, and peptide YY] and neurocrine (vasoactive intestinal peptide) peptides, and the synthetic glucocorticoid, dexamethasone, were without effect on secretion of the gut GLI peptides, at doses of 10(-12) to 10(-6) M. The results of the present study therefore demonstrate that secretion of the intestinal proglucagon-derived peptides is under the regulatory control of a wide variety of intestinal endocrine and neurocrine peptides, as well as nutrients (fats) and neurotransmitters (acetylcholine).
肠道胰高血糖素原衍生肽分泌的生理调节尚未得到充分研究。因此，我们使用了胎鼠肠道细胞培养模型，在体外研究其他肠道调节肽对肠道胰高血糖素样免疫反应性（GLI）肽分泌的控制。发现肠道内分泌肽胃抑制肽（浓度大于或等于10^(-10)M时，P<0.05）、神经分泌肽胃泌素释放肽（浓度大于或等于10^(-12)M时，P<0.05）和降钙素基因相关肽（浓度大于或等于10^(-8)M时，P<0.05）以剂量依赖性方式刺激肠道GLI肽的分泌。胃泌素释放肽及其两栖类等效物蛙皮素在刺激GLI肽分泌方面具有同等效力。相比之下，内分泌和神经分泌的肠道生长抑素相关肽，即生长抑素-28和-14，分别在浓度为10^(-10)（P<0.01）和10^(-8)（P<0.01）M时抑制GLI肽的释放，在10^(-10)M时检测到两种肽的效力存在显著差异（P<0.05）。生长抑素-28和-14的抑制作用均可通过用百日咳毒素预孵育细胞来阻断（P<0.05）。在用油酸钠（10^(-4)M；P<0.05）或胆碱能激动剂氨甲酰甲胆碱（浓度大于或等于100μM；P<0.05）处理培养细胞时，也检测到了肠道GLI肽分泌的剂量依赖性刺激。其他内分泌肽[胆囊收缩素、胰高血糖素、胰高血糖素样肽-1(1-37)、胰高血糖素样肽-1(7-37)、胰高血糖素样肽-2、神经降压素和肽YY]、神经分泌肽（血管活性肠肽）以及合成糖皮质激素地塞米松，在10^(-12)至10^(-6)M的剂量下对肠道GLI肽的分泌没有影响。因此，本研究结果表明，肠道胰高血糖素原衍生肽的分泌受到多种肠道内分泌和神经分泌肽以及营养物质（脂肪）和神经递质（乙酰胆碱）的调节控制。
