Won Justin G s, Tseng Hsiao-Shan, Yang An-Hang, Tang Kam-Tsun, Jap Tjin-Shing, Kwok Ching-Fai, Lee Chen Hsen, Lin Hong-Da
Department of Medicine, Veterans General Hospital-Taipei, Taiwan, Republic of China.
Metabolism. 2003 Oct;52(10):1320-9. doi: 10.1016/s0026-0495(03)00200-2.
The selective intra-arterial calcium stimulation test has greatly facilitated the precise regionalization of insulinomas smaller than 2 cm, which noninvasive techniques (ultrasound [US], computed tomography [CT], magnetic resonance imaging [MRI]) often fail to localize. This study examined not only the role of the test in the localization of insulinomas, but also the responsiveness of 3 beta-cell peptides (insulin, C peptide, and proinsulin) and their relationship to the degree of differentiation of the tumor cells, using percentage decrease of both proinsulin/insulin (P/I) and proinsulin/C peptide (P/C) ratios after stimulation as indices. Ten consecutive surgically proven insulinoma patients each received an injection of calcium into the arteries supplying the pancreas after standard selective angiography and beta-cell peptide levels were measured in samples taken from the right hepatic vein before and 30, 60, 90, 120, and 180 seconds after each injection prior to operation. After surgery, the expressions of the calcium sensing receptor (CaSR) on the resected tumors were assessed by immunohistochemistry. Intra-arterial calcium stimulation with sampling either for insulin or for C peptide correctly predicted the site of insulinoma in 8 of 9 patients or in 7 of 8 patients if the 2 big malignant insulinomas were excluded; thus, the detection rate of this test was 89% and 88%, respectively. Calcium administration stimulated a marked and prompt release of insulin and C peptide simultaneously. Both peaked within 30 to 60 seconds, then declined gradually thereafter, remaining above the baseline at 180 seconds. The magnitude of increase correlated well with the corresponding percentage decrease of P/I and P/C ratios. The response of proinsulin was much less. Immunohistochemistry demonstrated variable membraneous staining for CaSR in normal pancreatic islets and in about 9% of the total normal beta cells, whereas staining in tumor cells was only minimally detectable. We conclude that selective intra-arterial calcium stimulation with hepatic venous sampling either for insulin or for C peptide is a highly sensitive method for the preoperative localization of small insulinomas. Calcium injection stimulates a brisk response of insulin, C peptide, and proinsulin simultaneously and the magnitude of increase of both insulin and C peptide appears to be correlated well with the degree of differentiation of the tumor cells. The exact mechanism by which calcium provokes the release of beta-cell peptides is less clear and whether the CaSR is involved in the mechanism of its action requires further study.
选择性动脉内钙刺激试验极大地促进了对小于2 cm的胰岛素瘤进行精确的区域定位，而无创技术（超声[US]、计算机断层扫描[CT]、磁共振成像[MRI]）常常无法对其进行定位。本研究不仅考察了该试验在胰岛素瘤定位中的作用，还以刺激后胰岛素原/胰岛素（P/I）和胰岛素原/C肽（P/C）比值的下降百分比为指标，研究了3种β细胞肽（胰岛素、C肽和胰岛素原）的反应性及其与肿瘤细胞分化程度的关系。连续10例经手术证实的胰岛素瘤患者在标准选择性血管造影后，向供应胰腺的动脉内注射钙，并在术前每次注射前及注射后30、60、90、120和180秒从右肝静脉采集样本，测定β细胞肽水平。术后，通过免疫组织化学评估切除肿瘤上钙敏感受体（CaSR）的表达。如果排除2例大的恶性胰岛素瘤，动脉内注射钙并采集胰岛素或C肽样本，在9例患者中有8例或8例患者中有7例正确预测了胰岛素瘤的位置；因此，该试验的检测率分别为89%和88%。注射钙同时刺激胰岛素和C肽显著且迅速释放。两者均在30至60秒内达到峰值，随后逐渐下降，在180秒时仍高于基线水平。增加幅度与P/I和P/C比值相应的下降百分比密切相关。胰岛素原的反应则小得多。免疫组织化学显示，正常胰岛和大约9%的正常β细胞中CaSR有不同程度的膜染色，而肿瘤细胞中的染色仅勉强可检测到。我们得出结论，选择性动脉内钙刺激并肝静脉采集胰岛素或C肽样本是术前定位小胰岛素瘤的一种高度敏感的方法。注射钙同时刺激胰岛素、C肽和胰岛素原迅速反应，胰岛素和C肽的增加幅度似乎与肿瘤细胞的分化程度密切相关。钙引发β细胞肽释放的确切机制尚不清楚，CaSR是否参与其作用机制有待进一步研究。
