Islet amyloid polypeptide inhibits glucagon release and exerts a dual action on insulin release from isolated islets
Islet amyloid polypeptide inhibits glucagon release and exerts a dual action on insulin release from isolated islets
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DOI：
10.1016/s0167-0115(02)00252-5
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发表时间：
2003-03-28
影响因子：
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通讯作者：
Lundquist, I
中科院分区：
文献类型：
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作者：
Åkesson, B;Panagiotidis, G;Lundquist, I
我们研究了广泛浓度范围的胰岛淀粉样多肽（LAPP）对各种促分泌素刺激的胰高血糖素和胰岛素释放的影响。在无葡萄糖的胰岛培养液中，胰高血糖素释放速率高，我们观察到低浓度的IAPP，10（-10）和10（-8）M，对胰高血糖素释放有明显的抑制作用。类似地，由c-精氨酸、胆碱能激动剂卡巴胆碱或磷酸二酯酶抑制剂异丁基甲基黄嘌呤（IBMX）（环AMP系统的激活剂）刺激的胰高血糖素释放在10（-10）和10（-8）M浓度范围内被IAPP抑制。此外，基础胰高血糖素释放在7和10 mM葡萄糖抑制IAPP。相反，IAPP对胰岛素释放具有双重作用。因此，低浓度的IAPP在7 mM葡萄糖下引起基础胰岛素分泌的适度增加，并且还引起由卡巴胆碱刺激的胰岛素释放的适度增加。然而，高浓度的IAPP抑制由葡萄糖（10和16.7 mM）、IBMX、卡巴胆碱和L-精氨酸刺激的胰岛素释放。总之，我们的数据表明，IAPP作为胰高血糖素释放的抑制剂对胰岛激素分泌具有复杂的影响，并对胰岛素分泌具有双重作用，主要对刺激的胰岛素释放产生负反馈，对基础胰岛素释放产生正反馈。(C)2002 Elsevier Science B. V.保留所有权利。
We have studied the influence of a wide concentration range of islet amyloid polypeptide (LAPP) on both glucagon and insulin release stimulated by various types of secretagogues. In an islet incubation medium devoid of glucose, the rate of glucagon release being high, we observed a marked suppressive action by low concentrations of IAPP, 10(-10) and 10(-8) M, on glucagon release. Similarly, glucagon release stimulated by c-arginine, the cholinergic agonist carbachol, or the phosphodiesterase inhibitor isobutylmethyl xanthine (IBMX), an activator of the cyclic AMP system, was inhibited by IAPP in the 10(-10) and 10(-8) M concentration range. Moreover, basal glucagon release at 7 and 10 mM glucose was suppressed by IAPP. In contrast, IAPP exerted a dual action on insulin release. Hence, low concentrations of IAPP brought about a modest increase of basal insulin secretion at 7 mM glucose and also of insulin release stimulated by carbachol. High concentrations of IAPP, however, inhibited insulin release stimulated by glucose (10 and 16.7 mM), IBMX, carbachol and L-arginine. In conclusion, our data suggest that IAPP has complex effects on islet hormone secretion serving as an inhibitor of glucagon release and having a dual action on insulin secretion exerting mainly a negative feedback on stimulated and a positive feedback on basal insulin release. (C) 2002 Elsevier Science B.V. All rights reserved.