A 1 week IGF-1 infusion decreases arterial insulin concentrations but increases pancreatic insulin content and islet vascularity in fetal sheep

Abstract

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.

Keywords: Beta-cell; fetus; insulin; insulin-like growth factor; islet.

Figure 1

There was no correlation between fetal arterial plasma insulin concentrations in the IGF‐1 group with fetal arterial plasma glucose (A), oxygen (B), norepinephrine (C), or cortisol (D) concentrations. Individual control (■) and IGF‐1 (○) fetal data are plotted.

Figure 2

Pancreatic islet vessel density was measured by immune‐ and GITC‐conjugated GS‐1 staining and was higher in IGF‐1 fetuses (B) compared to Control fetuses (A). Costatining was performed for insulin (blue) as well as glucagon, somatostatin, and pancreatic polypeptide (red). (C) Data are mean ± SE for Control (n = 7) and IGF‐1 (n = 8) fetuses. *Indicates P < 0.05 by Students t test.