Glucocorticoid overexposure in neonatal life alters pancreatic beta-cell function in newborn foals1

Abstract

Studies in humans and animals have linked abnormal programming of adult tissue function to excess glucocorticoids during perinatal development. The current study investigated the hypothesis that physiological variations in glucocorticoid concentrations during early neonatal life of the foal alter the secretory responses of the pancreatic β cells 2 and 12 wk after treatment. Spontaneously delivered foals received either saline or long-acting ACTH for 5 d from 1 d after birth to maintain an endogenous rise in cortisol concentrations. Starting at d 10, pancreatic β cell function was studied using an intravenous (i.v.) glucose tolerance test, an i.v. arginine challenge, and an i.v. tolbutamide challenge. The maximum increment in plasma insulin achieved in response to exogenous glucose was less in ACTH-treated foals at both 2 and 12 wk of age (P<0.05). By 12 wk of age, developmental changes also occurred in the magnitude and biphasic pattern of glucose-stimulated insulin release. The area under the insulin curve during the early phase of insulin secretion (0 to 30 min) was not different between the 2- and 12-wk-old animals but was significantly greater during the later phase (30 to 120 min) at 12 wk than at 2 wk (P<0.05). Arginine infusion induced a brief 5 to 15 min increase in plasma concentrations of insulin that was not different in saline- and ACTH-treated foals. The β-cell response to tolbutamide infusion was rapid and monophasic, and there was no difference (P>0.05) in the area under the insulin curve with treatment at 2 or at 12 wk. However, after tolbutamide, plasma insulin concentrations remained increased for a longer period in the ACTH-treated than in the saline-treated foals at 12 wk of age (P<0.05). Hence, this is the first study to show altered pancreatic β-cell function after ACTH-induced glucocorticoid overexposure during early postnatal life in foals.

Effects of maternal dexamethasone treatment on pancreatic β cell function in the pregnant mare and post natal foal

“…Collectively, these observations suggest that dexamethasone can restrict fetal bone growth but may be less effective at inhibiting growth of fetal somatic tissues in horses than other species. This resembled the developmental profile of glucose-stimulated insulin secretion seen previously in foals of untreated mares [34]. The insulin responses of the foals to glucose were similar in the 2 treatment groups at both ages and resembled those published previously for age-matched foals of mares receiving no treatment [34].…”

“…In previous studies of dexamethasone administration, foal birthweight was also unaffected, although crown rump length was reduced at dexamethasone doses similar to those used here [6][7][8]. The insulin responses of the foals to glucose were similar in the 2 treatment groups at both ages and resembled those published previously for age-matched foals of mares receiving no treatment [34]. Collectively, these observations suggest that dexamethasone can restrict fetal bone growth but may be less effective at inhibiting growth of fetal somatic tissues in horses than other species.…”

Metabolic Profile of Broodmares During Late Pregnancy and Early Post‐Partum

“…; Jellyman et al. ). During pregnancy, mares develop increased sensitivity to glucose with an enhanced insulin resistance which can modify the supply of adequate glucose to the foetus (Ousey et al.…”

“…This result differs slightly from findings on BHB by Filipovic et al (2010), who found increased BHB concentrations only in early lactation. Previous studies showed that significant variations in carbohydrate metabolism and in pancreatic b-cell function occur in the broodmares during pregnancy (Fowden et al 1984;Ousey et al 2008;Jellyman et al 2013). During pregnancy, mares develop increased sensitivity to glucose with an enhanced insulin resistance which can modify the supply of adequate glucose to the foetus (Ousey et al 2008).…”

Maternal high-fat diet programs rat offspring hypertension and activates the adipose renin-angiotensin system

“…17-19 Notably, both maternal under- or over-nutrition results in offspring obesity and hypertension. 18,20-21 Despite this convincing evidence, there are no studies that have investigated the regulation of the adipogenic RAS in programmed, obesity-mediated hypertension. We hypothesized that the adipose tissue RAS is activated in the obese, hypertensive offspring that were exposed to maternal high fat diet during pregnancy and/or lactation.…”