High Co-Expression of the Ghrelin and LEAP2 Receptor GHSR with Pancreatic Polypeptide in Mouse and Human Islets

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dc.contributor.authorGupta, Deepalien
dc.contributor.authorDowsett, Georgina K. C.en
dc.contributor.authorMani, Bharath K.en
dc.contributor.authorShankar, Kripaen
dc.contributor.authorOsborne-Lawrence, Sherrien
dc.contributor.authorMetzger, Nathan P.en
dc.contributor.authorLam, Brian Y. H.en
dc.contributor.authorYeo, Giles S. H.en
dc.contributor.authorZigman, Jeffrey M.en
dc.date.accessioned2021-07-09T16:42:49Z
dc.date.available2021-07-09T16:42:49Z
dc.date.issued2021-07-09
dc.descriptionThe attached file includes supplementary tables and figures, This submission meets the Extended Data Sets and Supplemental Materials requirements that are included in author guidelines for Endocrinology (Print ISSN 0013-7227, Online ISSN 1945-7170).en
dc.description.abstractIslets represent an important site of direct action of the hormone ghrelin, with expression of the ghrelin receptor (growth hormone secretagogue receptor; GHSR) having been localized variably to alpha-cells, beta-cells, and/or somatostatin (SST)-secreting delta-cells. To our knowledge, GHSR expression by pancreatic polypeptide (PP)-expressing gamma-cells has not been specifically investigated. Here, histochemical analyses of Ghsr-IRES-Cre X Cre-dependent ROSA26-YFP reporter mice showed 85% of GHSR-expressing islet cells co-express PP, 50% co-express SST, and 47% co-express PP + SST. Analysis of single-cell transcriptomic data from mouse pancreas revealed 95% of Ghsr-expressing cells co-express Ppy, 100% co-express Sst, and 95% co-express Ppy + Sst. This expression was restricted to gamma-cell and delta-cell clusters. Analysis of several single-cell human pancreatic transcriptome datasets revealed 59% of GHSR-expressing cells co-express PPY, 95% co-express SST, and 57% co-express PPY + SST. This expression was prominent in delta-cell and beta-cell clusters, also occurring in other clusters including gamma-cells and alpha-cells. GHSR expression levels were upregulated by type 2 diabetes mellitus in beta-cells. In mice, plasma PP positively correlated with fat mass and with plasma levels of the endogenous GHSR antagonist/inverse agonist LEAP2. Plasma PP also elevated upon LEAP2 and synthetic GHSR antagonist administration. These data suggest that in addition to delta-cells, beta-cells, and alpha-cells, PP-expressing pancreatic cells likely represent important direct targets for LEAP2 and/or ghrelin in both mice and humans.en
dc.identifier.citationGupta D, Dowsett GKC, Mani BK, Shankar K, Osborne-Lawrence S, Metzger NP, Lam BYH, Yeo GSH, Zigman JM. Data from: High co-expression of the ghrelin and LEAP2 receptor GHSR with pancreatic polypeptide in mouse and human islets. UT Southwestern Institutional Repository 2021. Deposited 9 July 2021. https://hdl.handle.net/2152.5/9595en
dc.identifier.urihttps://hdl.handle.net/2152.5/9595
dc.language.isoenen
dc.titleHigh Co-Expression of the Ghrelin and LEAP2 Receptor GHSR with Pancreatic Polypeptide in Mouse and Human Isletsen
dc.typeDataseten

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