胃旁路术后严重高胰岛素血症性低血糖患者胰岛中胰高血糖素样肽-1 (GLP-1) 受体并未过度表达。
Glucagon-like peptide-1 (GLP-1) receptors are not overexpressed in pancreatic islets from patients with severe hyperinsulinaemic hypoglycaemia following gastric bypass.
机构信息
Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, PO Box 62, Murtenstrasse 31, CH-3010 Berne, Switzerland.
出版信息
Diabetologia. 2010 Dec;53(12):2641-5. doi: 10.1007/s00125-010-1901-y. Epub 2010 Sep 14.
AIMS/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) receptors are highly overexpressed in benign insulinomas, permitting in vivo tumour visualisation with GLP-1 receptor scanning. The present study sought to evaluate the GLP-1 receptor status in vitro in other pancreatic disorders leading to hyperinsulinaemic hypoglycaemia, specifically after gastric bypass surgery.
METHODS
Fresh frozen pancreatic tissue samples (n=7) from six gastric bypass surgery patients suffering from hyperinsulinaemic hypoglycaemia were evaluated for GLP-1 receptor content using in vitro receptor autoradiography, and compared with normal pancreas and with pancreatic insulinoma tissues.
RESULTS
GLP-1 receptor analysis of the pancreatic tissues, which histopathologically were compatible with nesidioblastosis and originated from post-bypass hypoglycaemic patients, revealed a mean density value of GLP-1 receptors in the islets of 1,483 ± 183 dpm/mg tissue. Pharmacological characterisation indicated the presence of specific GLP-1 receptors. The density of islet GLP-1 receptor in post-gastric bypass patients did not differ from that of normal pancreas (1,563 ± 104 dpm/mg tissue, n = 10). Receptor density in pancreatic acini was low in post-bypass and control conditions. In contrast, benign insulinomas showed a high density of GLP-1 receptors, with a mean value of 8,302 ± 1,073 dpm/mg tissue (n = 6).
CONCLUSIONS/INTERPRETATION: In contrast to insulinoma, hyperinsulinaemic hypoglycaemia after gastric bypass surgery is not accompanied by overexpression of GLP-1 receptor in individual islets. Thus, patients with post-gastric bypass hyperinsulinaemic hypoglycaemia are not candidates for GLP-1 receptor imaging in vivo using radiolabelled exendin. These GLP-1 receptor data support the notion that the islet pathobiology of post-gastric bypass hypoglycaemia is distinctly different from that of benign insulinomas.
目的/假设:胰高血糖素样肽-1(GLP-1)受体在良性胰岛素瘤中高度过表达,允许使用 GLP-1 受体扫描进行体内肿瘤可视化。本研究旨在评估导致高胰岛素血症性低血糖的其他胰腺疾病(特别是胃旁路手术后)的体外 GLP-1 受体状态。
方法
使用体外受体放射自显影术评估来自接受胃旁路手术的 6 例高胰岛素血症性低血糖患者的 7 例新鲜冷冻胰腺组织样本中 GLP-1 受体含量,并与正常胰腺和胰腺胰岛素瘤组织进行比较。
结果
对组织病理学上与 nesidioblastosis 相符且源自术后低血糖患者的胰腺组织进行 GLP-1 受体分析,结果显示胰岛中 GLP-1 受体的平均密度值为 1483 ± 183 dpm/mg 组织。药理学特征表明存在特异性 GLP-1 受体。胃旁路手术后患者的胰岛 GLP-1 受体密度与正常胰腺(1563 ± 104 dpm/mg 组织,n = 10)无差异。在胃旁路和对照条件下,胰腺腺泡中的受体密度均较低。相比之下,良性胰岛素瘤显示出 GLP-1 受体的高密度,平均值为 8302 ± 1073 dpm/mg 组织(n = 6)。
结论/解释:与胰岛素瘤不同,胃旁路手术后的高胰岛素血症性低血糖症并不会导致单个胰岛中 GLP-1 受体过度表达。因此,胃旁路手术后高胰岛素血症性低血糖症患者不适合使用放射性标记的 exendin 进行体内 GLP-1 受体成像。这些 GLP-1 受体数据支持这样的观点,即胃旁路手术后低血糖症的胰岛病理生物学与良性胰岛素瘤明显不同。