A Chronic Fetal Leucine Infusion Potentiates Fetal Insulin Secretion and Increases Pancreatic Islet Size, Vascularity, and β Cells in Late-Gestation Sheep.

摘要: BACKGROUND Infusion of a complete amino acid mixture into normal late-gestation fetal sheep potentiates glucose-stimulated insulin secretion (GSIS). Leucine acutely stimulates in and isolated islets vitro. OBJECTIVES We hypothesized that 9-d leucine infusion would potentiate GSIS sheep. METHODS Columbia-Rambouillet at 126 days gestation received to achieve 50%-100% increase concentrations or control infusion. At the end we measured GSIS, pancreatic morphology, expression mRNAs. Pancreatic islet endothelial cells (ECs) were from incubated with supplemental vascular growth factor A (VEGFA) followed by collection mRNA. Data multiple time points compared repeated-measures 2-factor ANOVA. 1 point using Student's t test Mann-Whitney test. RESULTS Glucose-stimulated 80% higher leucine-infused (LEU) fetuses than controls (P  5000 μm2 (75% more >5000 μm2; P < 0.05) larger proportion pancreas stained for β (12% greater; P < 0.05). vascularity both 25% greater LEU (P < 0.05). VEGFA hepatocyte (HGF) mRNA expressions 38% 200% (P < 0.05), respectively. In ECs, HGF was 20% 50% after incubation (P < 0.05) (P < 0.01), CONCLUSIONS demonstrating glucose act synergistically stimulate being comprised contributed GSIS.