Glucocorticoid overexposure in neonatal life alters pancreatic beta-cell function in newborn foals.

This research investigates the impact of excessive glucocorticoids on the function of pancreatic beta cells in newborn foals. The study shows that elevated glucocorticoid levels in the early neonatal period cause changes in insulin secretion responses over time, indicating a potential alteration in adult tissue function due to hormonal imbalances during perinatal development.

Study Rationale and Hypothesis

• The researchers were motivated by prior investigations that linked abnormal performance of adult tissues to excessive glucocorticoids during the perinatal development phase.
• The study hypothesized that variations in glucocorticoid concentration in a foal’s early neonatal life could modify the secretion patterns of pancreatic beta cells.

Methodology

• Newborn foals, born naturally, were administered either saline or long-acting ACTH over a period of 5 days starting from the day after birth. The aim was to keep an internal rise in cortisol levels.
• On the 10th day, the function of pancreatic beta cells was studied using intravenous glucose tolerance, arginine challenge, and tolbutamide challenge.

Findings

• ACTH-treated foals had a lesser increase in plasma insulin in response to exogenous glucose, observed at both 2 and 12 weeks of age.
• There were also developmental changes in the size and biphasic pattern of glucose-stimulated insulin release by 12 weeks.
• The insulin secretion during the early phase was not different between 2 and 12 weeks old foals, but it was significantly more during the later phase at 12 weeks than at 2 weeks.
• Arginine infusion led to a small increase in plasma insulin concentrations, which was the same for both ACTH and saline-treated foals.
• The response of β-cells to tolbutamide was fast and monophasic, and there was no difference in overall insulin secretion at 2 or at 12 weeks. However, post-tolbutamide, the ACTH-treated foals had higher plasma insulin concentrations for a longer duration compared to the saline-treated foals at week 12.

Conclusion

• From this study, it is concluded that overexposure to glucocorticoids triggered by ACTH during early postnatal life in foals alters the function of pancreatic beta cells. This appears to be the first study reporting such a phenomenon.