A short, 90‑minute infusion of the IGF‑1 LR3 peptide in fetal sheep quickly drops the amount of insulin the animals release, but once the pancreas cells are taken out and tested, they can still make normal amounts of insulin. This means the drop in insulin is temporary and not due to permanent damage to the insulin‑producing cells.

Insulin-like growth factor-1 (IGF-1) is a critical fetal growth hormone that has been proposed as a therapy for intrauterine growth restriction. We previously demonstrated that a 1-week IGF-1 LR3 infusion into fetal sheep reduces <i>in vivo</i> and <i>in vitro</i> insulin secretion suggesting an intrinsic islet defect. Our objective herein was to determine whether this intrinsic islet defect was related to chronicity of exposure. We therefore tested the effects of a 90-min IGF-1 LR3 infusion on fetal glucose-stimulated insulin secretion (GSIS) and insulin secretion from isolated fetal islets. We first infused late gestation fetal sheep (<i>n</i> = 10) with either IGF-1 LR3 (IGF-1) or vehicle control (CON) and measured basal insulin secretion and <i>in vivo</i> GSIS utilizing a hyperglycemic clamp. We then isolated fetal islets immediately following a 90-min IGF-1 or CON <i>in vivo</i> infusion and exposed them to glucose or potassium chloride to measure <i>in vitro</i> insulin secretion (IGF-1, <i>n</i> = 6; CON, <i>n</i> = 6). Fetal plasma insulin concentrations decreased with IGF-1 LR3 infusion (<i>P</i> &lt; 0.05), and insulin concentrations during the hyperglycemic clamp were 66% lower with IGF-1 LR3 infusion compared to CON (<i>P</i> &lt; 0.0001). Insulin secretion in isolated fetal islets was not different based on infusion at the time of islet collection. Therefore, we speculate that while acute IGF-1 LR3 infusion may directly suppress insulin secretion, the fetal &#x3b2;-cell <i>in vitro</i> retains the ability to recover GSIS. This may have important implications when considering the long-term effects of treatment modalities for fetal growth restriction.