Glucocorticoids and equine pancreatic β cell function

REASONS FOR PERFORMING STUDY: Synthetic glucocorticoids are used to treat inflammatory conditions in horses. In other pregnant animals, glucocorticoids are given to stimulate fetal maturation with long-term metabolic consequences for the offspring if given preterm. However, their metabolic effects during equine pregnancy remain unknown. OBJECTIVE: Thus, this study investigated the metabolic effects of dexamethasone administration on pregnant pony mares and their foals after birth. STUDY DESIGN: Experimental study. METHODS: A total of 3 doses of dexamethasone (200 μg/kg bwt i.m.) were given to 6 pony mares at 48 h intervals beginning at ≈270 days of pregnancy. Control saline injections were given to 5 mares using the same protocol. After fasting overnight, pancreatic β cell responses to exogenous glucose were measured in the mares before, during and after treatment. After birth, pancreatic β cell responses to exogenous glucose and arginine were measured in the foals at 2 and 12 weeks. RESULTS: In mares during treatment, dexamethasone but not saline increased basal insulin concentrations and prolonged the insulin response to exogenous glucose. Basal insulin and glucose concentrations still differed significantly between the 2 groups 72 h post treatment. Dexamethasone treatment significantly reduced placental area but had little effect on foal biometry at birth or subsequently. Foal β cell function at 2 weeks was unaffected by maternal treatment. However, by 12 weeks, pancreatic β cell sensitivity to arginine, but not glucose, was less in foals delivered by dexamethasone- than saline-treated mares. CONCLUSIONS: Dexamethasone administration induced changes in maternal insulin-glucose dynamics, indicative of insulin resistance and had subtle longer term effects on post natal β cell function of the foals. The programming effects of dexamethasone in horses may be mediated partially by altered maternal metabolism and placental growth.These studies were funded by the Horserace Betting Levy Board.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/evj.12560

Effects of birth weight, sex and neonatal glucocorticoid overexposure on glucose-insulin dynamics in young adult horses.

In several species, adult metabolic phenotype is influenced by the intrauterine environment, often in a sex-linked manner. In horses, there is also a window of susceptibility to programming immediately after birth but whether adult glucose-insulin dynamics are altered by neonatal conditions remains unknown. Thus, this study investigated the effects of birth weight, sex and neonatal glucocorticoid overexposure on glucose-insulin dynamics of young adult horses. For the first 5 days after birth, term foals were treated with saline as a control or ACTH to raise cortisol levels to those of stressed neonates. At 1 and 2 years of age, insulin secretion and sensitivity were measured by exogenous glucose administration and hyperinsulinaemic-euglycaemic clamp, respectively. Glucose-stimulated insulin secretion was less in males than females at both ages, although there were no sex-linked differences in glucose tolerance. Insulin sensitivity was greater in females than males at 1 year but not 2 years of age. Birth weight was inversely related to the area under the glucose curve and positively correlated to insulin sensitivity at 2 years but not 1 year of age. In contrast, neonatal glucocorticoid overexposure induced by adrenocorticotropic hormone (ACTH) treatment had no effect on whole body glucose tolerance, insulin secretion or insulin sensitivity at either age, although this treatment altered insulin receptor abundance in specific skeletal muscles of the 2-year-old horses. These findings show that glucose-insulin dynamics in young adult horses are sexually dimorphic and determined by a combination of genetic and environmental factors acting during early life.We would like to thank the staff of the University Biofacilities Service for their care of the animals. We are also grateful to the Horserace Betting Levy Board for their financial support

Investigation of an outbreak of tapeworm-associated colic in a training yard.

A novel serological assay which measures IgG(T) specific for a 12/13 kDa protein of the equine tapeworm Anoplocephala perfoliata was used as part of a colic outbreak investigation. A training/rehabilitation yard for Thoroughbreds and Arabs was found to have an increasing incidence of colic over a 5 year period, culminating in a peak incidence of 1.15 episodes/horse year at risk. Four animals suffered from ileal impaction colic which necessitated surgical management. A case-control study design suggested a strong association between tapeworm infection and colic, with evidence of a dose-response relationship. Intervention, in the form of anticestode anthelminthics, coincided with a decrease in the incidence of colic and a fall in anti-12/13 kDa IgG(T) antibody levels of 8 horses monitored post-treatment. This study demonstrates that anthelminthic regimens, using exclusively ivermectin, may lead to an increase in tapeworm infection intensity which may in turn lead to an increased incidence of colic. Furthermore, it provides support to the hypothesis that the risk of ileal impaction colic and spasmodic colic increases with tapeworm infection intensity. The practical application of the anti-12/13 kDa IgG(T) ELISA is demonstrated by this study

Investigation of an outbreak of tapeworm-associated colic in a training yard.

A novel serological assay which measures IgG(T) specific for a 12/13 kDa protein of the equine tapeworm Anoplocephala perfoliata was used as part of a colic outbreak investigation. A training/rehabilitation yard for Thoroughbreds and Arabs was found to have an increasing incidence of colic over a 5 year period, culminating in a peak incidence of 1.15 episodes/horse year at risk. Four animals suffered from ileal impaction colic which necessitated surgical management. A case-control study design suggested a strong association between tapeworm infection and colic, with evidence of a dose-response relationship. Intervention, in the form of anticestode anthelminthics, coincided with a decrease in the incidence of colic and a fall in anti-12/13 kDa IgG(T) antibody levels of 8 horses monitored post-treatment. This study demonstrates that anthelminthic regimens, using exclusively ivermectin, may lead to an increase in tapeworm infection intensity which may in turn lead to an increased incidence of colic. Furthermore, it provides support to the hypothesis that the risk of ileal impaction colic and spasmodic colic increases with tapeworm infection intensity. The practical application of the anti-12/13 kDa IgG(T) ELISA is demonstrated by this study