ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 65 P234 | DOI: 10.1530/endoabs.65.P234

Adhesion G-protein coupled receptors as novel players in islet development

Oladapo Edward Olaniru1, Patricio Atanes1, Klaudia Toczyska1, Xianhua Piao2 & Shanta Persaud1

1King’s College London, London, UK; 2Children’s Hospital and Harvard Medical School, Boston, USA

Adhesion GPCRs (aGPCRs) have been implicated in developmental processes and deletion of some aGPCRs in neonatal mice results in decreased β-cell differentiation capacity, leading to glucose intolerance in adult life. Here, we investigated the expression of aGPCR mRNAs in mouse islets and determined the expression and function of GPR56, the most abundant aGPCR in islets, in developing mouse pancreas. Quantitative PCR indicated that mouse islets expressed mRNAs encoding 26 of the 32 aGPCRs, with GPR56 being the most abundant of all islet aGPCRs, while 8 were expressed at only trace levels. GPR56 expression was approximately 15-fold higher than the next most highly expressed aGPCRs: CELSR1, GPR125, ELTD1 and LPHN1. RNAscope in-situ hybridization and immunohistochemistry revealed that GPR56 was strongly expressed by SOX9- and NGN3-positive mouse pancreas endocrine progenitors, with significantly increased expression at post-natal day 9 (P9), where beta-cell replication peaks (% area GPR56+ cells; E18: 0.15±0.05, P9: 0.47±0.07, n=10, P<0.01). In islets from P9 GPR56 knockout (KO) mice, the number of cells proliferating and remaining in the cell cycle was significantly lower than in age-matched WT mice (BrdU+Ki67+ cells/µm2; WT: 115.9±18.2, KO: 50.9±6.3, n=3, P<0.05), leading to less β-cells at this stage (% β-cells/islet; WT: 68.5±0.8, KO: 54.8±3.0, n=3, P<0.05), but higher numbers of α-cells in GPR56KO islets (% α-cells/islet; WT: 17.7±0.9, KO: 33.7±2.8, n=3, P<0.01). Our data support an important role for the abundant aGPCR GPR56 in islet development, indicating that it is required for an appropriate α-/β-cell ratio.

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