Subtype-selective expression of the five somatostatin receptors (hSSTR1-5)in human pancreatic islet cells - A quantitative double-label immunohistochemical analysis

We have developed a panel of rabbit polyclonal antipeptide antibodies again st the five human somatostatin receptor subtypes (hSSTR1-5) and used them t o 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. SST R5 was also an abundant isotype, being colocalized in 87% of beta-cells. SS TR2 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-cell s, and SSTR4 was absent, SSTR5 was preferentially expressed in 75% of SST-p ositive 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 s tudies reveal predominant expression of SSTR1, SSTR2, and SSTR5 in human is lets, (beta-Cells, alpha-cells, and delta-cells each express multiple SSTR isoforms, beta-cells being rich in SSTR1 Rad SSTR5, alpha-cells in SSTR2, a nd delta-cells in SSTR5. Although there is no absolute specificity of any S STR for an islet cell type, SSTR1 is beta-cell selective, and SSTR2 is alph a-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 c ell selectivity displayed by SSTR1 and SSTR2. Subtype-selective SSTR expres sion in islet cells could be the basis for preferential insulin suppression by SSTR1-specific ligands and of glucagon inhibition by SSTR2-selective co mpounds.