2154-P: Mice Fed a Low Protein Diet In Utero Show Decreased Apelin Receptor Presence in Ins⁺Glut2^Lo Cells during Pregnancy Associated with Lower ß-Cell Mass

The apelinergic system, consisting of the apelin receptor (APJ) and its cognate ligand apelin, is active in pancreas, skeletal muscle, adipose and other tissues. Apelin/APJ are implicated in energy metabolism as apelin is secreted by adipocytes and may bind APJ on β-cell membranes to reduce glucose-stimulated insulin secretion. Apelin-13 administration has been shown to increase islet cell mass and β-cell insulin content in mice with T1DM and can increase insulin sensitivity in obese, hyperinsulinaemic mice. The metabolic stress of pregnancy is normally accommodated by β-cell mass (BCM) expansion and increased glucose-stimulated insulin secretion. A failure to increase BCM can contribute to the risk of gestational diabetes. Exposure of mice to a low protein diet (LP) in utero can limit expansion of BCM during subsequent pregnancy. As previously shown, insulin-expressing but glucose-transporter-2-low (Ins⁺Glut2^Lo) progenitor cells contribute to gestational BCM expansion. Thus, we investigated how APJ presence on Ins+Glut2Lo cells might differ in islets of pregnant C57Bl/6 mice previously exposed to LP vs. control (C) diet. F1 female offspring exposed to LP or C diet in utero and postnatal development were time mated and pancreata collected at gestational days (GD) 9 and 12. Insulin, Glut2, and APJ were visualized by immunohistochemistry with respect to β-cell localization in small endocrine clusters (1-5 β-cells) and in islets (≥ 6 β-cells). The percentage of Ins⁺Glut2^LoAPJ⁺ cells relative to all Ins+ cells was significantly decreased in LP-exposed mice vs. C at GD12 (C 5.7±1.0%, LP 2.7±0.1%, p<0.05) when Ins⁺Glut2^Lo cell expansion is maximal, but not at GD9 (C 4.9±1.6%, LP 3.4±0.9%). Significant differences were not found in % Ins⁺Glut2^LoAPJ⁺ cells relative to extra-islet clusters or islets between LP vs. C at GD 9 and 12. Results suggest that APJ presence may contribute to BCM expansion during pregnancy mediated by Ins+Glut2Lo cells.