Fetal insulin is critical for regulation of growth. Insulin concentrations are partly determined by the amount of β-cells present and their insulin content. Insulin-like growth factor-1 (IGF-1) is a fetal anabolic growth factor which also impacts β-cell mass in models of β-cell injury and diabetes. The extent to which circulating concentrations of IGF-1 impact fetal β-cell mass and pancreatic insulin content is unknown. We hypothesized that an infusion of an IGF-1 analog for 1 week into the late gestation fetal sheep circulation would increase β-cell mass, pancreatic islet size, and pancreatic insulin content. After the 1-week infusion, pancreatic insulin concentrations were 80% higher than control fetuses (P < 0.05), but there were no differences in β-cell area, β-cell mass, or pancreatic vascularity. However, pancreatic islet vascularity was 15% higher in IGF-1 fetuses and pancreatic VEGFA, HGF, IGF1, and IGF2 mRNA expressions were 70-90% higher in IGF-1 fetuses compared to control fetuses (P < 0.05). Plasma oxygen, glucose, and insulin concentrations were 25%, 22%, and 84% lower in IGF-1 fetuses, respectively (P < 0.05). The previously described role for IGF-1 as a β-cell growth factor may be more relevant for local paracrine signaling in the pancreas compared to circulating endocrine signaling.
Pubmed ID: 30175552 RIS Download
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