Subtype-selective expression of the five somatostatin receptors (hSSTR1-5) in human pancreatic islet cells - A quantitative double-label immunohistochemical analysis
Subtype-selective expression of the five somatostatin receptors (hSSTR1-5) in human pancreatic islet cells - A quantitative double-label immunohistochemical analysis
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DOI：
10.2337/diabetes.48.1.77
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发表时间：
1999-01-01
期刊：
影响因子：
7.7
通讯作者：
Patel, YC
中科院分区：
文献类型：
--
作者：
Kumar, U;Sasi, R;Patel, YC
我们已经开发了一组兔抗人生长抑素受体亚型的多克隆抗肽抗体（hSSTR 1 -5），并用它们通过定量双标记共聚焦荧光免疫细胞化学分析hSSTR 1 -5在正常人胰岛细胞中的表达模式。所有五种hSSTR亚型均在胰岛中表达，SSTR免疫阳性细胞数的顺序为SSTR 1> SSTR 5> SSTR 2> SSTR 3> SSTR 4。在所有β细胞中，SSTR 1与胰岛素强烈共定位。SSTR 5也是一种丰富的同种型，共定位于87%的β细胞中。在46%的β细胞中发现SSTR 2，而SSTR 3和SSTR 4表达相对较差，SSTR 2与胰高血糖素在89%的α细胞中强烈共定位，而SSTR 5和8 STR 1分别与胰高血糖素在35%和26%的α细胞中共定位，SSTR 3在偶尔的α细胞中检测到，而SSTR 4不存在，SSTR 5优先表达在75%的SST阳性细胞中，并且是主要的δ细胞SSTR亚型，而SSTR 1 -3仅在少数δ细胞中共定位，并且SSTR 4不存在。这些研究揭示了SSTR 1、SSTR 2和SSTR 5在人胰岛中的主要表达。β-细胞、α-细胞和δ-细胞各自表达多种SSTR同种型，β-细胞富含SSTR 1和SSTR 5，α-细胞富含SSTR 2，δ-细胞富含SSTR 5。尽管任何SSTR对胰岛细胞类型都没有绝对的特异性，但SSTR 1是β细胞选择性的，SSTR 2是α细胞选择性的，SSTR 5在β细胞和δ细胞中良好表达，在α细胞中中度良好表达，因此它缺乏SSTR 1和SSTR 2所显示的胰岛细胞选择性。胰岛细胞中的亚型选择性SSTR表达可能是SSTR 1特异性配体优先抑制胰岛素和SSTR 2选择性化合物抑制胰高血糖素的基础。
We have developed a panel of rabbit polyclonal antipeptide antibodies against the five human somatostatin receptor subtypes (hSSTR1-5) and used them to analyze the pattern of expression of hSSTR1-5 in normal human islet cells by quantitative double-label confocal fluorescence immunocytochemistry All five hSSTR subtypes were variably expressed in islets, The number of SSTR immunopositive cells showed a rank order of SSTR1 > SSTR5 > SSTR2 > SSTR3 > SSTR4. SSTR1 was strongly colocalized with insulin in all (beta-cells. SSTR5 was also an abundant isotype, being colocalized in 87% of beta-cells. SSTR2 was found in 46% of beta-cells, whereas SSTR3 and SSTR4 were relatively poorly expressed, SSTR2 was strongly colocalized with glucagon in 89%, of alpha-cells, whereas SSTR5 and 8STR1 colocalized with glucagon in 35 and 26% of alpha-cells, respectively, SSTR3 was detected in occasional alpha-cells, and SSTR4 was absent, SSTR5 was preferentially expressed in 75% of SST-positive cells and was the principal delta-cell SSTR subtype, whereas SSTR1-3 were colocalized in only a few delta-cells, and SSTR4 was absent. These studies reveal predominant expression of SSTR1, SSTR2, and SSTR5 in human islets, (beta-Cells, alpha-cells, and delta-cells each express multiple SSTR isoforms, beta-cells being rich in SSTR1 Rad SSTR5, alpha-cells in SSTR2, and delta-cells in SSTR5. Although there is no absolute specificity of any SSTR for an islet cell type, SSTR1 is beta-cell selective, and SSTR2 is alpha-cell selective, SSTR5 is well expressed in beta-cells and delta-cells and moderately well expressed in alpha-cells, and thereby it lacks the islet cell selectivity displayed by SSTR1 and SSTR2. Subtype-selective SSTR expression in islet cells could be the basis for preferential insulin suppression by SSTR1-specific ligands and of glucagon inhibition by SSTR2-selective compounds.