Endocrine Abstracts (2017) 50 P324 | DOI: 10.1530/endoabs.50.P324

Leptin receptors localise to [beta]-cells in the fetal ovine pancreas, but do not appear to influence [beta]-cell mass in utero

Shelley Harris1, Sharon Raja1, Miles De Blasio2, FB Peter Wooding2, Dominique Blache3, Abigail Fowden2 & Alison Forhead1,2

1Oxford Brookes Universty, Oxford, UK; 2University of Cambridge, Cambridge, UK; 3University of Western Australia, Crawley, Australia.

Babies born to mothers with diabetes during pregnancy are exposed to high circulating leptin before birth and, in turn, are at increased risk of developing diabetes in later life. In pancreatic islets isolated from fetal sheep, leptin influences β-cell proliferation in a bimodal manner. This study examined the effect of exogenous leptin infusion and leptin receptor antagonism on pancreatic β-cell mass in the sheep fetus in vivo.

All procedures were performed under the UK Animals (Scientific Procedures) Act 1986. In 28 pregnant ewes at 118-120 days of gestation (d; term ˜145d), the femoral artery and vein of the fetus was catheterized under general anaesthesia. For 5 days from 125d, fetuses were infused i.v with either saline (2 ml/day, 0.9% NaCl, n=13), recombinant ovine leptin (LEP1, 0.6 mg/kg/day, n=8 or LEP2, 1.4 mg/kg/day, n=7) or recombinant ovine long-form leptin receptor antagonist (LRA, 4.6 mg/kg/day, n=5). Arterial blood was collected before and during treatment. After maternal and fetal euthanasia, the fetal pancreas was weighed and examined for leptin receptor expression and β-cell mass using immunohistochemistry and stereological point counting. Data were analysed by two-way ANOVA.

Leptin receptor protein was localised to the β-cells of the fetal ovine pancreas at 130d of gestation. Plasma concentrations of leptin were increased on all days of infusion in LEP1 and LEP2-treated fetuses (P<0.05). Neither leptin nor LRA infusion influenced fetal body weight, absolute or relative measurements of pancreas or β-cell mass.

The expression of leptin receptors in pancreatic β-cells of the sheep fetus indicates a role for leptin in islet development before birth. In this preliminary study, however, pancreatic β-cell mass was not affected by exogenous leptin infusion or antagonism of the long-form leptin receptor. Further investigation is required to assess whether leptin regulates pancreatic development and secretory function in utero with consequences for the offspring of diabetic pregnancies.

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