Zambre Y, Ling Z, Chen M C, Hou X, Woon C W, Culler M, Taylor J E, Coy D H, Van Schravendijk C, Schuit F, Pipeleers D G, Eizirik D L
Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
Biochem Pharmacol. 1999 May 15;57(10):1159-64. doi: 10.1016/s0006-2952(99)00010-6.
Somatostatin (SS)-14 and SS28 are produced by pancreatic D cells and gut mucosa and inhibit pancreatic islet insulin and glucagon release. There are five distinct SS receptor (SSTR) subtypes, namely SSTR1-5, which show different affinities for SS14 and SS28. In order to identify the subtype responsible for inhibition of insulin release by human B cells, SSTR-selective SS analogs were tested in isolated human islets. Glucose-stimulated insulin secretion in human islets incubated for 1 hr at 20 mM glucose, and in islets cultured for 24 hr at a near-physiological (6.1 mM) glucose concentration, was inhibited (<50% of the control) by SSTR5-specific analogs and by SS14 and SS28. SS14, SS28, and different SSTR5 preferential analogs also inhibited islet amyloid polypeptide release during the 24-hr culture. On the other hand, a group of SSTR2-selective analogs failed to inhibit insulin release. Analysis by reverse transcription-polymerase chain reaction indicated that human islets express similar amounts of SSTR2 and SSTR5 mRNAs, while human pancreatic ductal cells express much lower levels of these mRNAs. In conclusion, our data suggest that SSTR5 is an important mediator of the insulin inhibitory action of SS in cultured human islets.
生长抑素（SS）-14和SS28由胰腺D细胞和肠道黏膜产生，可抑制胰岛胰岛素和胰高血糖素的释放。有五种不同的SS受体（SSTR）亚型，即SSTR1 - 5，它们对SS14和SS28表现出不同的亲和力。为了确定负责抑制人B细胞胰岛素释放的亚型，在分离的人胰岛中测试了SSTR选择性SS类似物。在20 mM葡萄糖下孵育1小时的人胰岛以及在接近生理浓度（6.1 mM）葡萄糖下培养24小时的胰岛中，葡萄糖刺激的胰岛素分泌被SSTR5特异性类似物以及SS14和SS28抑制（<对照的50%）。SS14、SS28和不同的SSTR5优先类似物在24小时培养期间也抑制胰岛淀粉样多肽的释放。另一方面，一组SSTR2选择性类似物未能抑制胰岛素释放。逆转录 - 聚合酶链反应分析表明，人胰岛表达相似量的SSTR2和SSTR5 mRNA，而人胰腺导管细胞表达的这些mRNA水平要低得多。总之，我们的数据表明SSTR5是SS在培养的人胰岛中胰岛素抑制作用的重要介质。
