TY - JOUR
T1 - Subtype-selective expression of the five somatostatin receptors (hSSTR1- 5) in human pancreatic islet cells
T2 - A quantitative double-label immunohistochemical analysis
AU - Kumar, Ujendra
AU - Sasi, Ramakrishnan
AU - Suresh, Sundar
AU - Patel, Amit
AU - Thangaraju, Muthusamy
AU - Metrakos, Peter
AU - Patel, Shutish C.
AU - Patel, Yogesh C.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1999/1
Y1 - 1999/1
N2 - 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 β-cells. SSTR5 was also an abundant isotype, being colocalized in 87% of β-cells. SSTR2 was found in 46% of β-cells, whereas SSTR3 and SSTR4 were relatively poorly expressed. SSTR2 was strongly colocalized with glucagon in 89% of α-cells, whereas SSTR5 and SSTR1 colocalized with glucagon in 35 and 26% of α-cells, respectively. SSTR3 was detected in occasional α-cells, and SSTR4 was absent. SSTR5 was preferentially expressed in 75% of SST-positive cells and was the principal δ-cell SSTR subtype, whereas SSTR1-3 were colocalized in only a few δ-cells, and SSTR4 was absent. These studies reveal predominant expression of SSTR1, SSTR2, and SSTR5 in human islets. β-Cells, α-cells, and δ-cells each express multiple SSTR isoforms, β-cells being rich in SSTR1 and SSTR5, α-cells in SSTR2, and δ-cells in SSTR5. Although there is no absolute specificity of any SSTR for an islet cell type, SSTR1 is β-cell selective, and SSTR2 is α-cell selective. SSTR5 is well expressed in β- cells and δ-cells and moderately well expressed in α-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.
AB - 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 β-cells. SSTR5 was also an abundant isotype, being colocalized in 87% of β-cells. SSTR2 was found in 46% of β-cells, whereas SSTR3 and SSTR4 were relatively poorly expressed. SSTR2 was strongly colocalized with glucagon in 89% of α-cells, whereas SSTR5 and SSTR1 colocalized with glucagon in 35 and 26% of α-cells, respectively. SSTR3 was detected in occasional α-cells, and SSTR4 was absent. SSTR5 was preferentially expressed in 75% of SST-positive cells and was the principal δ-cell SSTR subtype, whereas SSTR1-3 were colocalized in only a few δ-cells, and SSTR4 was absent. These studies reveal predominant expression of SSTR1, SSTR2, and SSTR5 in human islets. β-Cells, α-cells, and δ-cells each express multiple SSTR isoforms, β-cells being rich in SSTR1 and SSTR5, α-cells in SSTR2, and δ-cells in SSTR5. Although there is no absolute specificity of any SSTR for an islet cell type, SSTR1 is β-cell selective, and SSTR2 is α-cell selective. SSTR5 is well expressed in β- cells and δ-cells and moderately well expressed in α-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.
UR - http://www.scopus.com/inward/record.url?scp=0032908805&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032908805&partnerID=8YFLogxK
U2 - 10.2337/diabetes.48.1.77
DO - 10.2337/diabetes.48.1.77
M3 - Article
C2 - 9892225
AN - SCOPUS:0032908805
SN - 0012-1797
VL - 48
SP - 77
EP - 85
JO - Diabetes
JF - Diabetes
IS - 1
ER -