Abstract
Glucagon-like-peptide-1 (GLP1) analogs may induce thyroid or pancreatic diseases in animals, raising questions about their use in diabetic patients. There is, however, controversy regarding expression of GLP1 receptors (GLP1R) in human normal and diseased thyroid and pancreas. Here, 221 human thyroid and pancreas samples were analyzed for GLP1R immunohistochemistry and compared with quantitative in vitro GLP1R autoradiography. Neither normal nor hyperplastic human thyroids containing parafollicular C cells express GLP1R with either method. Papillary thyroid cancer do not, and medullary thyroid carcinomas rarely express GLP1R. Insulin- and somatostatin-producing cells in the normal pancreas express a high density of GLP1R, whereas acinar cells express them in low amounts. Ductal epithelial cells do not express GLP1R. All benign insulinomas express high densities of GLP1R, whereas malignant insulinomas rarely express them. All ductal pancreatic carcinomas are GLP1R negative, whereas 6/20 PanIN 1/2 and 0/12 PanIN 3 express GLP1R. Therefore, normal thyroid, including normal and hyperplastic C cells, or papillary thyroid cancer are not targets for GLP1 analogs in humans. Conversely, all pancreatic insulin- and somatostatin-producing cells are physiological GLP1 targets, as well as most acini. As normal ductal epithelial cells or PanIN 3 or ductal pancreatic carcinomas do not express GLP1R, it seems unlikely that GLP1R is related to neoplastic transformation in pancreas. GLP1R-positive medullary thyroid carcinomas and all benign insulinomas are candidates for in vivo GLP1R targeting.
摘要
胰高血糖素样肽-1(GLP1)类似物可能诱发了动物的甲状腺或胰腺疾病,这提示它们是否在糖尿病患者中发挥了作用。然而,在正常和患病的人甲状腺和胰腺中胰高血糖素样肽-1受体(GLP1R)的表达是有争议的。这里,我们用免疫组化的方法检测了221例人甲状腺和胰腺标本中GLP1R的表达,并与体外GLP1R定量放射自显影进行比较。在包含滤泡旁C细胞的正常和增生甲状腺用这两种方法均未检测到GLP1R的表达。甲状腺乳头状癌检测不到GLP1R表达,很少量的甲状腺髓样癌能检测到表达。在正常胰腺中,胰岛素与生长抑素分泌细胞表达较强的GLP1R,然而腺泡细胞表达较弱,导管上皮细胞不表达。所有良性的胰岛素瘤表达很强的GLP1R,然而在恶性胰岛素瘤中很少表达。所有胰腺癌是GLP1R阴性,而6/20例胰腺上皮内瘤变1、2级和0/12例胰腺上皮内瘤变3级表达GLP1R。因此,正常甲状腺,包括正常和增生的C细胞和乳头状甲状腺癌不是胰高血糖素样肽-1(GLP1)类似物的靶组织。相反,所有胰岛素与生长抑素分泌细胞还有绝大部分腺泡细胞在生理学上是GLP1的靶细胞。由于正常导管上皮细胞、胰腺上皮内瘤变3级和胰腺癌中不表达GLP1R,可能GLP1R与胰腺肿瘤恶性转化无关。GLP1R阳性的甲状腺髓样癌和所有良性胰岛素瘤是体内GLP1R的候选靶组织。
共0条评论