Department of General Paediatrics, Neonatology and Paediatric Cardiology, University Children's Hospital Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany.
Diabetologia. 2013 Jan;56(1):31-5. doi: 10.1007/s00125-012-2750-7. Epub 2012 Oct 17.
AIMS/HYPOTHESIS: Exercise-induced hyperinsulinism (EIHI) is a hypoglycaemic disorder characterised by inappropriate insulin secretion following anaerobic exercise or pyruvate load. Activating promoter mutations in the MCT1 gene (also known as SCLA16A1), coding for monocarboxylate transporter 1 (MCT1), were shown to associate with EIHI. Recently, transgenic Mct1 expression in pancreatic beta cells was shown to introduce EIHI symptoms in mice. To date, MCT1 has not been demonstrated in insulin-producing cells from an EIHI patient.
In vivo insulin secretion was studied during an exercise test before and after the resection of an insulinoma. The presence of MCT1 was analysed using immunohistochemistry followed by laser scanning microscopy, western blot analysis and real-time RT-PCR of MCT1. The presence of MCT1 protein was analysed in four additional insulinoma patients.
Clinical testing revealed massive insulin secretion induced by anaerobic exercise preoperatively, but not postoperatively. MCT1 protein was not detected in the patient's normal islets. In contrast, immunoreactivity was clearly observed in the insulinoma tissue. Western blot analysis and real-time RT-PCR showed a four- to fivefold increase in MCT1 in the insulinoma tissue of the EIHI patient compared with human pancreatic islets. MCT1 protein was detected in three of four additional insulinomas.
CONCLUSIONS/INTERPRETATION: We show for the first time that an MCT1-expressing insulinoma was associated with EIHI and that MCT1 might be present in most insulinomas. Our data suggest that MCT1 expression in human insulin-producing cells can lead to EIHI and warrant further studies on the role of MCT1 in human insulinoma patients.
目的/假设：运动诱导性高胰岛素血症（EIHI）是一种低血糖障碍，其特征是在无氧运动或丙酮酸负荷后胰岛素分泌不当。已经表明，编码单羧酸转运蛋白 1（MCT1）的 MCT1 基因启动子突变与 EIHI 相关。最近，在胰腺β细胞中转基因 Mct1 的表达被证明会在小鼠中引入 EIHI 症状。迄今为止，尚未在 EIHI 患者的胰岛素产生细胞中证明 MCT1 的存在。
在胰岛素瘤切除前后的运动试验中研究体内胰岛素分泌情况。使用免疫组织化学法，然后使用激光扫描显微镜、western blot 分析和实时 RT-PCR 分析 MCT1 的存在。对另外四名胰岛素瘤患者进行了 MCT1 蛋白分析。
临床检查显示术前无氧运动可引起大量胰岛素分泌，但术后不行。患者正常胰岛中未检测到 MCT1 蛋白。相比之下，在胰岛素瘤组织中则清楚地观察到免疫反应性。Western blot 分析和实时 RT-PCR 显示，与人类胰腺胰岛相比，EIHI 患者的胰岛素瘤组织中 MCT1 增加了四到五倍。在另外四个胰岛素瘤中，有三个检测到了 MCT1 蛋白。
结论/解释：我们首次表明，表达 MCT1 的胰岛素瘤与 EIHI 相关，并且 MCT1 可能存在于大多数胰岛素瘤中。我们的数据表明，人胰岛素产生细胞中 MCT1 的表达可能导致 EIHI，并需要进一步研究 MCT1 在人类胰岛素瘤患者中的作用。
