Corticotropin releasing hormone can selectively stimulate glucose uptake in corticotropinoma via glucose transporter 1.
Corticotropin releasing hormone can selectively stimulate glucose uptake in corticotropinoma via glucose transporter 1.
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DOI：
10.1016/j.mce.2017.10.003
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发表时间：
2018-07-15
影响因子：
4.1
通讯作者：
Chittiboina P
中科院分区：
文献类型：
--
作者：
Lu J;Montgomery BK;Chatain GP;Bugarini A;Zhang Q;Wang X;Edwards NA;Ray-Chaudhury A;Merrill MJ;Lonser RR;Chittiboina P
术前检测促肾上腺皮质激素（ACTH）分泌引起库欣病（CD）的微腺瘤可改善手术效果。目前最好的磁共振成像不能检测到高达40%的微腺瘤。18f -氟脱氧葡萄糖（18F-FDG）正电子发射断层扫描（PET）是特异性的，但在检测糖皮质瘤时不敏感。理论上，促肾上腺皮质激素释放激素（CRH）刺激促分泌剂可以提高18F-FDG PET对腺瘤的检测。先前同时刺激CRH的尝试未能证明糖皮质瘤中18F-FDG摄取增加。我们假设促肾上腺皮质激素刺激导致糖皮质瘤患者葡萄糖摄取延迟升高。分析CRH对改善18FDG-PET对CD患者糖皮质瘤的检测效果。对手术标本进行葡萄糖转运蛋白1 （GLUT1）免疫反应性检测。在体外，对来自这些肿瘤的活细胞进行了促分泌作用（比色法葡萄糖摄取）和细胞内葡萄糖的命运（糖酵解应激分析）测试。用at -20细胞验证离体结果。CRH增加了人源性促皮质肿瘤细胞和at -20的葡萄糖摄取，但在正常小鼠或人促皮质细胞中没有增加（p<0.0001）。连续和间歇（1小时）CRH暴露增加at -20的葡萄糖摄取，在4小时时效果最大（p≤0.001）。同样，CRH和8-Br-cAMP在2h时导致GLUT1强烈上调和膜易位增加，而fasentin抑制基线（p<0.0001）和CRH介导的葡萄糖摄取。意料之中的是，术中收集的皮质瘤显示GLUT1过表达。最后，人源性促皮质肿瘤细胞表现出糖酵解增加和低糖氧化。促肾上腺皮质激素介导的葡萄糖摄取增加和延迟在腺瘤性促肾上腺皮质激素中发生差异。延迟分泌刺激的18F-FDG PET可提高微腺瘤的检出率。
Pre-operative detection of corticotropin (ACTH) secreting microadenomas causing Cushing's disease (CD) improves surgical outcomes. Current best magnetic resonance imaging fails to detect up to 40% of these microadenomas. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is specific, but not sensitive in detecting corticotropinomas. Theoretically, secretagogue stimulation with corticotropin releasing hormone (CRH) could improve detection of adenomas with 18F-FDG PET. Previous attempts with simultaneous CRH stimulation have failed to demonstrate increased 18F-FDG uptake in corticotropinomas. We hypothesized that CRH stimulation leads to a delayed elevation in glucose uptake in corticotropinomas. Clinical data was analyzed for efficacy of CRH in improving 18FDG-PET detection of corticotropinomas in CD. Glucose transporter 1 (GLUT1) immunoreactivity was performed on surgical specimens. Ex-vivo, viable cells from these tumors were tested for secretagogue effects (colorimetric glucose uptake), and for fate of intracellular glucose (glycolysis stress analysis). Validation of ex-vivo findings was performed with AtT-20 cells. CRH increased glucose uptake in human-derived corticotroph tumor cells and AtT-20, but not in normal murine or human corticotrophs (p<0.0001). Continuous and intermittent (1h) CRH exposure increased glucose uptake in AtT-20 with maximal effect at 4h (p≤0.001). Similarly, CRH and 8-Br-cAMP led to robust GLUT1 upregulation and increased membrane translocation at 2h, while fasentin suppressed baseline (p<0.0001) and CRH-mediated glucose uptake. Expectedly, intra-operatively collected corticotropinomas demonstrated GLUT1 overexpression. Lastly, human derived corticotroph tumor cells demonstrated increased glycolysis and low glucose oxidation. Increased and delayed CRH-mediated glucose uptake differentially occurs in adenomatous corticotrophs. Delayed secretagogue-stimulated 18F-FDG PET could improve microadenoma detection.
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影响因子：
5.8
作者：
BOCHICCHIO, D;LOSA, M;TEASDALE, GM
通讯作者：
TEASDALE, GM
影响因子：
--
作者：
Miller, AL;Webb, MS;Thompson, EB
通讯作者：
Thompson, EB
影响因子：
19.7
作者：
DESOUZA, B;BRUNETTI, A;DICHIRO, G
通讯作者：
DICHIRO, G
影响因子：
5.8
作者：
Moro, M;Putignano, P;Cavagnini, F
通讯作者：
Cavagnini, F
影响因子：
3.6
作者：
Iredale, PA;Duman, RS
通讯作者：
Duman, RS