At birth, the endocrine pancreas must assume a glucoregulatory role if the neonate is to survive the transition from parenteral to enteral nutrition. In species like the horse, neonatal hypoglycaemia is common, which suggests that the glucoregulatory mechanisms are not always fully competent at birth. Hence, this study examined pancreatic cell function in newborn foals during nutritional adaptation over the first 10 days post partum. Over a 48 h period at three time intervals after birth (days 1-2, 5-6 and 9-10 post partum), the cell responses to suckling and to intravenous administration of glucose, arginine and saline were measured in seven normal pony foals. Basal plasma concentrations of proinsulin, but not insulin or glucose, increased significantly between days 1 and 10. Suckling caused a gradual increase in plasma glucose, which was accompanied by a significant increase in plasma insulin concentrations 15 min after the onset of suckling on days 5 and 9, but not day 1. There was no significant change in plasma proinsulin concentrations in response to suckling at any age. At all ages studied, glucose and arginine administration stimulated an increase in the plasma concentrations of insulin and proinsulin; these cell responses did not change significantly with postnatal age. The insulin responses to glucose were significantly greater than those of arginine at each time period. Glucose clearance was significantly slower on day 1 than subsequently. Proinsulin and glucose, but not insulin, concentrations decreased significantly after saline administration at all three ages. At each time period, there was a significant positive relationship between the plasma insulin and proinsulin concentrations, the slope of which was significantly shallower on days 1-2 than subsequently. These results show that equine cells are responsive to glucose and arginine and release both insulin and proinsulin during the immediate postnatal period. They also suggest that newborn foals may be insulin resistant on the first day after birth.

SummaryReasons for performing study: During the switch from parenteral to enteral nutrition at birth, endocrine glands such as the pancreas must assume a glucoregulatory role for the first time if the neonate is to survive the transition to extrauterine life. Objectives: To determine the adaptations in pancreatic endocrine function during the neonatal period in term pony foals delivered by different methods. Methods: By measuring insulin and glucagon concentrations, pancreatic a and b cell responses to exogenous glucose (0.5 g/kg bwt) and arginine (100 mg/kg bwt) and to endogenous muzzling for 90 min were determined periodically over the first 10 post natal days in foals born spontaneously (n = 8) or by induction of labour with oxytocin at term (n = 7). Results: Pancreatic a and b cell function changed with post natal age in a manner related to the method of delivery. Induced foals had 2-3 fold greater b cell responses to exogenous glucose and arginine, despite similar glucose and a-amino nitrogen clearances compared with spontaneously delivered foals. Pancreatic b cell responses to glucose decreased by 50% while those to arginine doubled with increasing age in induced but not spontaneously delivered foals. In contrast, pancreatic a cell responses to arginine doubled with increasing age in foals born spontaneously but not by induction. These differences in pancreatic endocrine cell function with delivery method were associated with 2-3 fold higher cortisol levels in the induced foals and with differences in the absolute and age-related changes in basal concentrations of glucose, a-amino nitrogen and insulin. Conclusions: Induced delivery leads to changes in pancreatic b cell sensitivity to glucose and/or tissue insulin resistance in association with persistent neonatal hypercortisolaemia. Potential relevance: The altered post natal development of pancreatic endocrine function with induced delivery may compromise glucoregulation and adaptation to enteral nutrition in neonatal foals with potential consequences long after birth.

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.

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SummaryReasons for performing the study: The effects of overexposure to glucocorticoids during early life of the foal on the subsequent HPA programming of the hypothalamic-pituitary-adrenal axis are unknown. Objectives: To test the hypotheses that excess glucocorticoid exposure in early life subsequently increases both basal plasma concentrations of cortisol and the adrenocortical responsiveness to exogenous adrenocorticotropic hormone (ACTH). Methods: Foals received either saline (0.9% NaCl, n = 9) or long-acting ACTH (0.125 mg i.m. b.i.d., n = 6) for 5 days from Day 1 to increase endogenous cortisol concentrations. Long-term indwelling catheters were inserted under local anaesthesia into the jugular veins of foals aged 2 and 12 weeks. After recovery, short-acting ACTH1-24 was given as a single i.v. injection (2 mg/kg bwt) and blood samples were taken at 5-30 min intervals before and after ACTH administration to measure plasma cortisol concentrations. Results: Basal plasma cortisol concentrations were higher in ACTH-than in saline-treated foals at age 3 weeks, but not at 13 weeks. There were no significant differences in either the time profile or the area under the cortisol curve in response to ACTH between the 2 groups. Conclusions: These data suggest that ACTH-induced overexposure to glucocorticoids during early post natal life of the foal does not have a programming effect on HPA axis function at 13 weeks. In foals, the effects of ACTH-induced overexposure to glucocorticoids, if any, may not become apparent until much later in life in a long-lived species such as the horse. Potential relevance: These studies suggest that clinical and other stressful conditions that raise plasma cortisol concentrations during early life are unlikely to programme cardiovascular and metabolic function in horses in the short term.