PMID- 30081043 OWN - NLM STAT- MEDLINE DCOM- 20190715 LR - 20190715 IS - 1873-5169 (Electronic) IS - 0196-9781 (Linking) VI - 107 DP - 2018 Sep TI - RFamide-related peptide-3 promotes alpha TC1 clone 6 cell survival likely via GPR147. PG - 39-44 LID - S0196-9781(18)30141-4 [pii] LID - 10.1016/j.peptides.2018.07.009 [doi] AB - Type 2 diabetes mellitus (T2DM) is closely related to islet alpha cell mass and viability. Several types of RFamide-related peptides (RFRPs) are involved in regulating proliferation and function of islet cells. However, current understanding of the role of RFamide-related peptide-3 (RFRP-3) in pancreatic alpha cells is limited. Therefore, we investigated the expression of the RFRP-3 receptor, G protein-coupled receptor 147 (GPR147), in mouse islets and alpha TC1 clone 6 cells, and evaluated the function of RFRP-3 on alpha cells. We show that GPR147 is expressed in mouse islets and alpha cell lines. In addition, RFRP-3 promotes survival of alpha cells under conditions of hyperglycemia and serum starvation. Mechanistic evidence demonstrates that RFRP-3 activated PI3K/AKT and ERK1/2 signaling cascades and treatment with an antagonist of GPR147, 1-adamantanecarbonyl-Arg-Phe-NH(2) (RF9) blocked this function. These findings indicate a novel effect of RFRP-3 in promoting alpha cell survival, likely via GPR147. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Zhang, Wencheng AU - Zhang W AD - Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, 169 Changle Road West, 710032, China. FAU - Wang, Li AU - Wang L AD - Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, 169 Changle Road West, 710032, China. FAU - Yu, Xinwen AU - Yu X AD - Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, 169 Changle Road West, 710032, China. FAU - Jia, Aihua AU - Jia A AD - Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, 169 Changle Road West, 710032, China. FAU - Ming, Jie AU - Ming J AD - Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, 169 Changle Road West, 710032, China. FAU - Ji, Qiuhe AU - Ji Q AD - Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, 169 Changle Road West, 710032, China. Electronic address: qiuheji@hotmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180803 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Neuropeptides) RN - 0 (RFamide peptide) RN - 0 (Receptors, Neuropeptide) RN - 0 (neuropeptide FF receptor) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) SB - IM MH - Animals MH - Cell Proliferation MH - Cell Survival MH - Cells, Cultured MH - Glucagon-Secreting Cells/*metabolism/physiology MH - MAP Kinase Signaling System MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Neuropeptides/*metabolism/physiology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Receptors, Neuropeptide/*metabolism/physiology MH - *Signal Transduction OTO - NOTNLM OT - 1-adamantanecarbonyl-Arg-Phe-NH(2)(RF9) OT - G protein-coupled receptor 147 (GPR147) OT - Gonadotropin inhibitory hormone (GnIH) OT - RFamide-related peptide-3 (RFRP-3) EDAT- 2018/08/07 06:00 MHDA- 2019/07/16 06:00 CRDT- 2018/08/07 06:00 PHST- 2018/04/12 00:00 [received] PHST- 2018/07/08 00:00 [revised] PHST- 2018/07/31 00:00 [accepted] PHST- 2018/08/07 06:00 [pubmed] PHST- 2019/07/16 06:00 [medline] PHST- 2018/08/07 06:00 [entrez] AID - S0196-9781(18)30141-4 [pii] AID - 10.1016/j.peptides.2018.07.009 [doi] PST - ppublish SO - Peptides. 2018 Sep;107:39-44. doi: 10.1016/j.peptides.2018.07.009. Epub 2018 Aug 3.