Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Sci Rep. 2018 Jan 15;8(1):748. doi: 10.1038/s41598-017-18855-0.
Multiple endocrine neoplasia type 1 (MEN1) is an endocrine tumor syndrome caused by heterozygous mutations in the MEN1 tumor suppressor gene. The MEN1 pancreas of the adolescent gene carrier frequently contain diffusely spread pre-neoplasias and microadenomas, progressing to macroscopic and potentially malignant pancreatic neuroendocrine tumors (P-NET), which represents the major death cause in MEN1. The unveiling of the molecular mechanism of P-NET which is not currently understood fully to allow the optimization of diagnostics and treatment. Glucagon-like peptide 1 (GLP-1) pathway is essential in islet regeneration, i.e. inhibition of β-cell apoptosis and enhancement of β-cell proliferation, yet involvement of GLP-1 in MEN1 related P-NET has not yet been demonstrated. The objective of this work was to investigate if normal sized islets of Men1 heterozygous mice have increased Glucagon-like peptide-1 receptor (GLP-1R) expression compared to wild type islets, and if this increase is detectable in vivo with positron emission tomography (PET) using [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 (68Ga-Exendin-4). 68Ga-Exendin-4 showed potential for early lesion detection in MEN1 pancreas due to increased GLP1R expression.
多发性内分泌肿瘤 1 型（MEN1）是一种内分泌肿瘤综合征，由 MEN1 肿瘤抑制基因的杂合突变引起。青少年基因携带者的 MEN1 胰腺中经常存在弥漫性扩散的前肿瘤和微腺瘤，进展为宏观和潜在恶性的胰腺神经内分泌肿瘤（P-NET），这是 MEN1 的主要死亡原因。目前尚未完全了解 P-NET 的分子机制，无法优化诊断和治疗。胰高血糖素样肽 1（GLP-1）途径对于胰岛再生至关重要，即抑制β细胞凋亡和增强β细胞增殖，但 GLP-1 是否参与 MEN1 相关的 P-NET 尚未得到证实。这项工作的目的是研究 Men1 杂合子小鼠的正常大小胰岛与野生型胰岛相比是否表达增加的胰高血糖素样肽-1 受体（GLP-1R），并且这种增加是否可以通过正电子发射断层扫描（PET）使用[68Ga]Ga-DO3A-VS-Cys40-Exendin-4（68Ga-Exendin-4）在体内检测到。由于 GLP1R 表达增加，68Ga-Exendin-4 显示出在 MEN1 胰腺中早期检测病变的潜力。
