Proglucagon-Derived Peptides Do Not Significantly Affect Acute Exocrine Pancreas in Rats.
Proglucagon-Derived Peptides Do Not Significantly Affect Acute Exocrine Pancreas in Rats.
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DOI：
10.1097/mpa.0000000000000585
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发表时间：
2016-08
期刊：
影响因子：
2.9
通讯作者：
Bloom SR
中科院分区：
文献类型：
--
作者：
Akalestou E;Christakis I;Solomou AM;Minnion JS;Rutter GA;Bloom SR
有报告表明，使用胰升糖素样肽1(GLP-1)类似物治疗与增加胰腺炎风险之间存在联系。作为GLP-1和胰升糖素受体的双重激动剂，oxyntomodlin目前正在作为一种潜在的抗肥胖疗法进行研究，但对其胰腺安全性了解甚少。本研究的目的是研究氧合酶调节蛋白和其他胰高血糖素原衍生的多肽对大鼠外分泌胰腺的急性作用。麻醉大鼠静脉注射GLP-1、氧合调节蛋白、胰高血糖素和Exendin-4，检测血浆淀粉酶浓度的变化。此外，还测定了各多肽对大鼠胰腺腺泡细胞(AR42J)和原代分离的导管细胞的淀粉酶释放和增殖的影响。与赋形剂和胆囊收缩素(CCK)相比，多肽输注后血浆淀粉酶没有增加；然而，当与CCK联合给药时，氧合酶调节蛋白抑制了血浆淀粉酶。这些多肽都没有引起腺泡和导管细胞的增殖率或淀粉酶分泌的显著增加。当单独给药时，所研究的多肽对胰腺外分泌的增殖和血浆淀粉酶没有急性影响。氧合酶调节蛋白似乎是淀粉酶释放的有效抑制剂，与GLP-1激动剂相比，它可能使其成为一种更安全的针对胰腺炎的抗肥胖剂。
Reports have suggested a link between treatment with glucagon-like peptide 1 (GLP-1) analogues and an increased risk of pancreatitis. Oxyntomodulin, a dual agonist of both GLP-1 and glucagon receptors, is currently being investigated as a potential anti-obesity therapy, but little is known about its pancreatic safety. The aim of this study was to investigate the acute effect of oxyntomodulin and other proglucagon-derived peptides on the rat exocrine pancreas. GLP-1, oxyntomodulin, glucagon and exendin-4 were infused into anaesthetised rats to measure plasma amylase concentration changes. Additionally, the effect of each peptide on both amylase release and proliferation in rat pancreatic acinar (AR42J) and primary isolated ductal cells was determined. Plasma amylase did not increase post peptide infusion, compared to vehicle and cholecystokinin (CCK); however, oxyntomodulin inhibited plasma amylase when co-administered with CCK. None of the peptides caused a significant increase in proliferation rate or amylase secretion from acinar and ductal cells. The investigated peptides do not have an acute effect on the exocrine pancreas with regard to proliferation and plasma amylase, when administered individually. Oxyntomodulin appears to be a potent inhibitor of amylase release, potentially making it a safer anti-obesity agent regarding pancreatitis, compared to GLP-1 agonists.