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Article: Secreted PDZD2 exerts an insulinotropic effect on INS-1E cells by a PKA-dependent mechanism

TitleSecreted PDZD2 exerts an insulinotropic effect on INS-1E cells by a PKA-dependent mechanism
Authors
KeywordsPDZD2
Secreted PDZD2
INS-1E
Insulin
PKA
Issue Date2020
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/mce
Citation
Molecular and Cellular Endocrinology, 2020, v. 518, p. article no. 111026 How to Cite?
AbstractSecreted PDZD2 (sPDZD2) is a signaling molecule generated upon proteolytic processing of the multi-PDZ-containing protein PDZD2. Previous analysis of gene-trap mice deficient in the synthesis of full-length PDZD2, but not the secreted form, revealed a role of PDZD2 in the regulation of glucose-stimulated insulin secretion. Here, using the pancreatic INS-1E β cells as in vitro model, we showed that depletion of PDZD2/sPDZD2 by RNA interference suppressed the expression of β-cell genes Ins1, Glut2 and MafA whereas treatment with recombinant sPDZD2 rescued the suppressive effect. Similar to GLP-1, sPDZD2 stimulated intracellular cAMP levels, activated β-cell gene expression in a PKA-dependent manner and induced the phosphorylation and nuclear localization of PDX1. Depletion of PDX1 inhibited the sPDZD2 insulinotropic effect, which could also be demonstrated in mouse islets. In summary, our findings are consistent with sPDZD2 serving a signaling function in regulating β-cell gene expression.
Persistent Identifierhttp://hdl.handle.net/10722/290059
ISSN
2019 Impact Factor: 3.871
2015 SCImago Journal Rankings: 2.116
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSo, DHF-
dc.contributor.authorChan, JCY-
dc.contributor.authorTsui, MG-
dc.contributor.authorTsang, PSW-
dc.contributor.authorYao, KM-
dc.date.accessioned2020-10-22T08:21:30Z-
dc.date.available2020-10-22T08:21:30Z-
dc.date.issued2020-
dc.identifier.citationMolecular and Cellular Endocrinology, 2020, v. 518, p. article no. 111026-
dc.identifier.issn0303-7207-
dc.identifier.urihttp://hdl.handle.net/10722/290059-
dc.description.abstractSecreted PDZD2 (sPDZD2) is a signaling molecule generated upon proteolytic processing of the multi-PDZ-containing protein PDZD2. Previous analysis of gene-trap mice deficient in the synthesis of full-length PDZD2, but not the secreted form, revealed a role of PDZD2 in the regulation of glucose-stimulated insulin secretion. Here, using the pancreatic INS-1E β cells as in vitro model, we showed that depletion of PDZD2/sPDZD2 by RNA interference suppressed the expression of β-cell genes Ins1, Glut2 and MafA whereas treatment with recombinant sPDZD2 rescued the suppressive effect. Similar to GLP-1, sPDZD2 stimulated intracellular cAMP levels, activated β-cell gene expression in a PKA-dependent manner and induced the phosphorylation and nuclear localization of PDX1. Depletion of PDX1 inhibited the sPDZD2 insulinotropic effect, which could also be demonstrated in mouse islets. In summary, our findings are consistent with sPDZD2 serving a signaling function in regulating β-cell gene expression.-
dc.languageeng-
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/mce-
dc.relation.ispartofMolecular and Cellular Endocrinology-
dc.subjectPDZD2-
dc.subjectSecreted PDZD2-
dc.subjectINS-1E-
dc.subjectInsulin-
dc.subjectPKA-
dc.titleSecreted PDZD2 exerts an insulinotropic effect on INS-1E cells by a PKA-dependent mechanism-
dc.typeArticle-
dc.identifier.emailYao, KM: kmyao@hku.hk-
dc.identifier.authorityYao, KM=rp00344-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.mce.2020.111026-
dc.identifier.pmid32919022-
dc.identifier.scopuseid_2-s2.0-85091234615-
dc.identifier.hkuros317370-
dc.identifier.volume518-
dc.identifier.spagearticle no. 111026-
dc.identifier.epagearticle no. 111026-
dc.identifier.isiWOS:000584381600059-
dc.publisher.placeIreland-
dc.identifier.issnl0303-7207-

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