TY - JOUR
T1 - C-type natriuretic peptide receptor expression in pancreatic alpha cells
AU - Burgess, Matthew D.
AU - Moore, Kim D.
AU - Carter, Gay M.
AU - Alli, Abdel A.
AU - Granda, Christopher S.
AU - Ichii, Hirohito
AU - Ricordi, Camillo
AU - Gower, William R.
N1 - Funding Information:
Acknowledgments This work was supported by Merit Review Grants from the United State Department of Veterans AVairs (William R. Gower) and NIH for General Clinical Research Center MO1RR16587, 1RO1-DK55347 (Camillo Ricordi) and National Institute of Diabetes and Digestive and Kidney Diseases grant DK-41301 (Antibody/RIA Core). We acknowledge the excellent technical assistance by Candace Miranda and Adrenna Roberts.
PY - 2009/7
Y1 - 2009/7
N2 - Atrial natriuretic peptide (ANP), brain type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) comprise a family of natriuretic peptides that mediate their biological effects through three natriuretic peptide receptor subtypes, NPR-A (ANP, BNP), NPR-B (CNP) and NPR-C (ANP, BNP, CNP). Several reports have provided evidence for the expression of ANP and specific binding sites for ANP in the pancreas. The purpose of this study was to identify the ANP receptor subtype and to localize its expression to a specific cell type in the human pancreas. NPR-C immunoreactivity, but neither ANP nor NPR-A, was detected in human islets by immunofluorescent staining. No immunostaining was observed in the exocrine pancreas or ductal structures. Double-staining revealed that NPR-C was expressed mainly in the glucagon-containing alpha cells. NPR-C mRNA and protein were detected in isolated human islets by RT-PCR and Western blot analysis, respectively. NPR-C expression was also detected by immunofluorescent staining in glucagonoma but not in insulinoma. ANP, as well as BNP and CNP, stimulated glucagon secretion from perifused human islets (1,111 ± 55% vs. basal [7.3 fmol/min]; P < 0.001). This response was mimicked by cANP(4-23), a selective agonist of NPR-C. In conclusion, the NPR-C receptor is expressed in normal and neoplastic human alpha cells. These findings suggest a role for natriuretic peptides in the regulation of glucagon secretion from human alpha cells.
AB - Atrial natriuretic peptide (ANP), brain type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) comprise a family of natriuretic peptides that mediate their biological effects through three natriuretic peptide receptor subtypes, NPR-A (ANP, BNP), NPR-B (CNP) and NPR-C (ANP, BNP, CNP). Several reports have provided evidence for the expression of ANP and specific binding sites for ANP in the pancreas. The purpose of this study was to identify the ANP receptor subtype and to localize its expression to a specific cell type in the human pancreas. NPR-C immunoreactivity, but neither ANP nor NPR-A, was detected in human islets by immunofluorescent staining. No immunostaining was observed in the exocrine pancreas or ductal structures. Double-staining revealed that NPR-C was expressed mainly in the glucagon-containing alpha cells. NPR-C mRNA and protein were detected in isolated human islets by RT-PCR and Western blot analysis, respectively. NPR-C expression was also detected by immunofluorescent staining in glucagonoma but not in insulinoma. ANP, as well as BNP and CNP, stimulated glucagon secretion from perifused human islets (1,111 ± 55% vs. basal [7.3 fmol/min]; P < 0.001). This response was mimicked by cANP(4-23), a selective agonist of NPR-C. In conclusion, the NPR-C receptor is expressed in normal and neoplastic human alpha cells. These findings suggest a role for natriuretic peptides in the regulation of glucagon secretion from human alpha cells.
KW - Alpha cells
KW - Anp
KW - Glucagon
KW - Islets of langerhans
KW - Npr-c
KW - Pancreas
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U2 - 10.1007/s00418-009-0591-3
DO - 10.1007/s00418-009-0591-3
M3 - Article
C2 - 19352691
AN - SCOPUS:67349255005
VL - 132
SP - 95
EP - 103
JO - Zeitschrift für Zellforschung und Mikroskopische Anatomie. Abteilung Histochemie
JF - Zeitschrift für Zellforschung und Mikroskopische Anatomie. Abteilung Histochemie
SN - 0948-6143
IS - 1
ER -