Impaired insulin and incretin secretion underlie abnormal glucose tolerance (AGT) in pancreatic insufficient cystic fibrosis (PI-CF). Whether the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) can enhance pancreatic islet function in CF is not known. We studied 32 adults with PI-CF and AGT randomized to receive either GLP-1 (n=16) or GIP (n=16) during glucose-potentiated arginine (GPA) testing of islet function on two occasions with either incretin or placebo infused by randomized, double-blind, cross-over fashion. Another 4 adults with PI-CF and normal glucose tolerance (NGT) and 4 matched non-CF controls underwent similar assessment with GIP. In PI-CF with AGT, GLP-1 substantially augmented second-phase insulin secretion, but without effect on the acute insulin response to GPA or the proinsulin secretory ratio (PISR), while GIP infusion did not enhance second phase or GPA-induced insulin secretion but increased the PISR. GIP also did not enhance second-phase insulin in PI-CF with NGT but did so markedly in non-CF controls. These data indicate that GLP-1, but not GIP, augments glucose-dependent insulin secretion in PI-CF, supporting the likelihood that GLP-1 agonists could have therapeutic benefit in this population. Understanding loss of GIP's insulinotropic action in PI-CF may lead to novel insights into diabetes pathogenesis.

中文翻译：

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GLP-1 和 GIP 对葡萄糖不耐受、胰腺功能不全囊性纤维化患者胰岛功能的影响

胰岛素和肠促胰岛素分泌受损是胰腺囊性纤维化不足（PI-CF）中糖耐量异常（AGT）的基础。肠促胰岛素激素胰高血糖素样肽-1 (GLP-1) 和葡萄糖依赖性促胰岛素多肽 (GIP) 是否可以增强 CF 中的胰岛功能尚不清楚。我们研究了 32 名患有 PI-CF 和 AGT 的成年人，在两次注射肠促胰岛素或安慰剂的胰岛功能葡萄糖强化精氨酸 (GPA) 测试中随机接受 GLP-1 (n=16) 或 GIP (n=16)通过随机、双盲、交叉方式。另外 4 名患有 PI-CF 且糖耐量正常 (NGT) 的成人和 4 名匹配的非 CF 对照者接受了与 GIP 类似的评估。在具有 AGT 的 PI-CF 中，GLP-1 显着增强第二相胰岛素分泌，但对 GPA 的急性胰岛素反应或胰岛素原分泌比 (PISR) 没有影响，而 GIP 输注不会增强第二相或 GPA 诱导的胰岛素分泌但增加 PISR。GIP 也没有增强 PI-CF 中 NGT 的第二相胰岛素，但在非 CF 对照中效果显着。这些数据表明，GLP-1（而非 GIP）增强 PI-CF 中葡萄糖依赖性胰岛素分泌，支持 GLP-1 激动剂在该人群中具有治疗益处的可能性。了解 PI-CF 中 GIP 促胰岛素作用的丧失可能会给糖尿病发病机制带来新的见解。