PMID- 34326390 OWN - NLM STAT- MEDLINE DCOM- 20211213 LR - 20240403 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 11 IP - 1 DP - 2021 Jul 29 TI - Ontology of the apelinergic system in mouse pancreas during pregnancy and relationship with beta-cell mass. PG - 15475 LID - 10.1038/s41598-021-94725-0 [doi] LID - 15475 AB - The apelin receptor (Aplnr) and its ligands, Apelin and Apela, contribute to metabolic control. The insulin resistance associated with pregnancy is accommodated by an expansion of pancreatic beta-cell mass (BCM) and increased insulin secretion, involving the proliferation of insulin-expressing, glucose transporter 2-low (Ins(+)Glut2(LO)) progenitor cells. We examined changes in the apelinergic system during normal mouse pregnancy and in pregnancies complicated by glucose intolerance with reduced BCM. Expression of Aplnr, Apelin and Apela was quantified in Ins(+)Glut2(LO) cells isolated from mouse pancreata and found to be significantly higher than in mature beta-cells by DNA microarray and qPCR. Apelin was localized to most beta-cells by immunohistochemistry although Aplnr was predominantly associated with Ins(+)Glut2(LO) cells. Aplnr-staining cells increased three- to four-fold during pregnancy being maximal at gestational days (GD) 9-12 but were significantly reduced in glucose intolerant mice. Apelin-13 increased beta-cell proliferation in isolated mouse islets and INS1E cells, but not glucose-stimulated insulin secretion. Glucose intolerant pregnant mice had significantly elevated serum Apelin levels at GD 9 associated with an increased presence of placental IL-6. Placental expression of the apelinergic axis remained unaltered, however. Results show that the apelinergic system is highly expressed in pancreatic beta-cell progenitors and may contribute to beta-cell proliferation in pregnancy. CI - (c) 2021. The Author(s). FAU - Strutt, Brenda AU - Strutt B AD - Lawson Health Research Institute, St Joseph Health Care, 268 Grosvenor St, London, ON, N6A 4V2, Canada. FAU - Szlapinski, Sandra AU - Szlapinski S AD - Lawson Health Research Institute, St Joseph Health Care, 268 Grosvenor St, London, ON, N6A 4V2, Canada. AD - Department of Physiology and Pharmacology, Western University, London, ON, N6A 3K7, Canada. FAU - Gnaneswaran, Thineesha AU - Gnaneswaran T AD - Department of Physiology and Pharmacology, Western University, London, ON, N6A 3K7, Canada. FAU - Donegan, Sarah AU - Donegan S AD - Department of Physiology and Pharmacology, Western University, London, ON, N6A 3K7, Canada. FAU - Hill, Jessica AU - Hill J AD - Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW, UK. FAU - Bennett, Jamie AU - Bennett J AD - Lawson Health Research Institute, St Joseph Health Care, 268 Grosvenor St, London, ON, N6A 4V2, Canada. AD - Life Sciences Program, School of Interdisciplinary Science, McMaster University, Hamilton, ON, L8S 4LD, Canada. FAU - Hill, David J AU - Hill DJ AUID- ORCID: 0000-0002-2490-5678 AD - Lawson Health Research Institute, St Joseph Health Care, 268 Grosvenor St, London, ON, N6A 4V2, Canada. david.hill@lawsonresearch.com. AD - Department of Physiology and Pharmacology, Western University, London, ON, N6A 3K7, Canada. david.hill@lawsonresearch.com. AD - Departments of Medicine and Paediatrics, Western University, London, ON, N6A 3K7, Canada. david.hill@lawsonresearch.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210729 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Apelin) RN - 0 (Apelin Receptors) RN - 0 (Insulin) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Interleukin-6) RN - 0 (apelin-13 peptide) RN - 0 (interleukin-6, mouse) SB - IM MH - Animals MH - Apelin/metabolism MH - Apelin Receptors/metabolism MH - Cell Proliferation MH - Cell Separation MH - Female MH - Flow Cytometry MH - Gene Expression Profiling MH - Glucose Intolerance MH - Insulin/*metabolism MH - Insulin Resistance MH - Insulin-Secreting Cells/*metabolism MH - Intercellular Signaling Peptides and Proteins/metabolism MH - Interleukin-6/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Oligonucleotide Array Sequence Analysis MH - Pancreas/*embryology MH - Placenta/metabolism MH - Pregnancy MH - *Pregnancy, Animal PMC - PMC8322410 COIS- The study funders were not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report. The authors had no financial or professional conflicts of interest with the funding agencies. EDAT- 2021/07/31 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/07/29 CRDT- 2021/07/30 06:14 PHST- 2021/04/11 00:00 [received] PHST- 2021/07/15 00:00 [accepted] PHST- 2021/07/30 06:14 [entrez] PHST- 2021/07/31 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/07/29 00:00 [pmc-release] AID - 10.1038/s41598-021-94725-0 [pii] AID - 94725 [pii] AID - 10.1038/s41598-021-94725-0 [doi] PST - epublish SO - Sci Rep. 2021 Jul 29;11(1):15475. doi: 10.1038/s41598-021-94725-0.