Characterization of OATP1B3 and OATP2B1 transporter expression in the islet of the adult human pancreas
Characterization of OATP1B3 and OATP2B1 transporter expression in the islet of the adult human pancreas
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DOI：
10.1007/s00418-017-1580-6
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发表时间：
2017-10-01
影响因子：
2.3
通讯作者：
Schwarz, Ute I.
中科院分区：
文献类型：
--
作者：
Kim, Michelle;Deacon, Perri;Schwarz, Ute I.
有机阴离子转运多肽（ooatp）是一种膜蛋白，可介导细胞摄取结构多样的内源性和外源性化合物，包括胆盐、甲状腺激素和性激素、药物和毒素。oops在人类肝脏中的作用已经得到了很好的证实。我们最近的报告表明肝转运体OATP1B3存在于人β细胞中。本研究的目的是更好地表征成人胰岛中OATP1B3表达的细胞定位和个体间变异，作为年龄、性别和胰腺疾病的功能，并评估其他oatp的表达。在离体成人胰岛中观察到高水平的OATP1B3、OATP2B1、OATP1A2转录，但不表达OATP1B1。虽然OATP1B3蛋白的表达是可变的，但在10名受试者的正常胰腺组织的胰岛中，载体与胰高血糖素阳性α细胞的共定位频率高于与胰岛素阳性β细胞的共定位。此外，OATP1B3与内分泌细胞共染色在老年（60岁）受试者中比年轻（< 60岁）受试者高2 - 3倍。相比之下，在三个个体的子集中，OATP2B1主要在β细胞中发现，这表明OATP1B3和OATP2B1在胰岛中有不同的表达模式。胰岛及胰腺炎或胰腺腺癌病变组织的导管细胞中也可见丰富的OATP1B3染色。考虑到β和α细胞中关键OATP载体的丰度，OATP转运在胰岛细胞功能中的潜在影响可能被提出。未来的研究需要深入了解其具体的内分泌作用以及药理意义。
Organic anion-transporting polypeptides (OATPs) are membrane proteins that mediate cellular uptake of structurally diverse endogenous and exogenous compounds, including bile salts, thyroid and sex hormones, pharmacological agents, and toxins. Roles of OATPs in human liver are well established. Our recent report suggested the presence of the hepatic transporter OATP1B3 in human beta cells. The aim of this study was to better characterize cellular localization and interindividual variation in OATP1B3 expression in human adult islets as a function of age, sex, and pancreatic disease, and to assess the expression of other OATPs. High transcript levels of OATP1B3, OATP2B1, OATP1A2, but not OATP1B1 were observed in isolated human adult islets. While OATP1B3 protein expression was variable, the carrier co-localized more frequently with glucagon-positive alpha cells than insulin-positive beta cells in islets of normal pancreatic tissues from ten subjects using dual immunostaining. Moreover, OATP1B3 co-staining with endocrine cells was two- to three-fold higher in older (ae60 years) than younger (< 60 years) subjects. In comparison, in a subset of three individuals, OATP2B1 was primarily found in beta cells, suggesting a distinct expression pattern for OATP1B3 and OATP2B1 in islets. Abundant OATP1B3 staining was also observed in islet as well as ductal cells of diseased tissues of patients with pancreatitis or pancreatic adenocarcinoma. Considering the abundance of key OATP carriers in beta and alpha cells, potential implications of OATP transport in islet cell function may be suggested. Future studies are needed to gain insights into their specific endocrine roles as well as pharmacological relevance.