Down-regulation of pancreatic and duodenal homeobox-1 by somatostatin receptor subtype 5: A novel mechanism for inhibition of cellular proliferation and insulin secretion by somatostatin

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Abstract

Somatostatin (SST) is a regulatory peptide and acts as an endogenous inhibitory regulator of the secretory and proliferative responses of target cells. SST's actions are mediated by a family of seven transmembrane domain G protein-coupled receptors that comprise five distinct subtypes (SSTR1-5). SSTR5 is one of the major SSTRs in the islets of Langerhans. Homeodomain-containing transcription factor pancreatic and duodenal homeobox-1 (PDX-1) is essential for pancreatic development, β cell differentiation, maintenance of normal β cell functions in adults and tumorigenesis. Recent studies show that SSTR5 acts as a negative regulator for PDX-1 expression and that SSTR5 mediates somatostatin's inhibitory effect on cell proliferation and insulin expression/excretion through down-regulating PDX-1 expression. SSTR5 exerts its inhibitory effect on PDX-1 expression at both the transcriptional level by down-regulating PDX-1 mRNA and the post-translational level by enhancing PDX-1 ubiquitination. Identification of PDX-1 as a transcriptional target for SSTR5 may help in guiding the choice of therapeutic cancer treatments. © 2014 Zhou, Sinnett-Smith, Liu, Yu, Wu, Sanchez, Pandol, Abrol, Nemunaitis, Rozengurt and Brunicardi.

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Zhou, G., Sinnett-Smith, J., Liu, S. H., Yu, J., Wu, J., Sanchez, R., … Brunicardi, F. C. (2014). Down-regulation of pancreatic and duodenal homeobox-1 by somatostatin receptor subtype 5: A novel mechanism for inhibition of cellular proliferation and insulin secretion by somatostatin. Frontiers in Physiology. Frontiers Research Foundation. https://doi.org/10.3389/fphys.2014.00226

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