Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance.
Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance.
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DOI：
10.2337/db16-0394
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发表时间：
2017-01
期刊：
影响因子：
7.7
通讯作者：
Rickels MR
中科院分区：
文献类型：
--
作者：
Sheikh S;Gudipaty L;De Leon DD;Hadjiliadis D;Kubrak C;Rosenfeld NK;Nyirjesy SC;Peleckis AJ;Malik S;Stefanovski D;Cuchel M;Rubenstein RC;Kelly A;Rickels MR
胰腺功能不全的囊性纤维化（PI-CF）患者患糖尿病的风险增加。我们分别通过葡萄糖强化精氨酸和混合膳食耐量试验（MMTT）测定了具有正常糖耐量的胰腺充分囊性纤维化（PS-CF）、PI-CF和正常对照受试者的β细胞分泌能力和胰岛素分泌率，以便识别早期病理生理缺陷。在禁食、230 mg/dL 和 340 mg/dL 高血糖钳夹条件下测定急性胰岛细胞分泌反应。与 PS-CF 和正常对照受试者相比，PI-CF 受试者的急性胰岛素、C 肽和胰高血糖素反应较低，表明 β 细胞分泌能力和 α 细胞功能降低。 PI-CF 中葡萄糖增强期间的空腹胰岛素原与 C 肽和胰岛素原分泌比率较高，表明胰岛素原加工受损。在MMTT的前30分钟，与PS-CF和正常对照受试者相比，PI-CF的胰岛素分泌较低，与PS-CF相比，胰高血糖素样肽1和抑胃多肽较低，180分钟后，与正常对照受试者相比，PI-CF的血糖较高。这些研究结果表明，尽管糖耐量“正常”，但患有 PI-CF 的青少年和成人的功能性胰岛质量和相关的早期胰岛素分泌受损，这与肠促胰岛素反应降低可能导致 CF 餐后高血糖的早期发展。
Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined β-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fibrosis (PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance, in order to identify early pathophysiologic defects. Acute islet cell secretory responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia clamp conditions. PI-CF subjects had lower acute insulin, C-peptide, and glucagon responses compared with PS-CF and normal control subjects, indicating reduced β-cell secretory capacity and α-cell function. Fasting proinsulin-to-C-peptide and proinsulin secretory ratios during glucose potentiation were higher in PI-CF, suggesting impaired proinsulin processing. In the first 30 min of the MMTT, insulin secretion was lower in PI-CF compared with PS-CF and normal control subjects, and glucagon-like peptide 1 and gastric inhibitory polypeptide were lower compared with PS-CF, and after 180 min, glucose was higher in PI-CF compared with normal control subjects. These findings indicate that despite “normal” glucose tolerance, adolescents and adults with PI-CF have impairments in functional islet mass and associated early-phase insulin secretion, which with decreased incretin responses likely leads to the early development of postprandial hyperglycemia in CF.
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影响因子：
3.8
作者：
Coriati, Adele;Ziai, Sophie;Rabasa-Lhoret, Remi
通讯作者：
Rabasa-Lhoret, Remi
影响因子：
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作者：
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影响因子：
3.5
作者：
Dobson, L;Sheldon, CD;Hattersley, AT
通讯作者：
Hattersley, AT
影响因子：
3.5
作者：
Mohan, K.;Miller, H.;Walshaw, M.
通讯作者：
Walshaw, M.