Amino acid supplementation does not alter whole-body phenylalanine kinetics in Arabian geldings.

Stable isotope infusion methods have not been extensively used in horses to study protein metabolism. The objectives were to develop infusion and sampling methodologies for [1-(13)C] phenylalanine and apply these methods to determine whether the addition of supplemental amino acids to a control diet affected whole-body phenylalanine kinetics in mature horses. Arabian geldings were studied using a 6-h primed (9 µmol/kg), constant (6 µmol · kg(-1) · h(-1)) i.v. infusion of L-[1-(13)C] phenylalanine, with blood and breath sampled every 30 min, to measure whole-body phenylalanine kinetics in response to receiving the control diet (n = 12) or the control diet supplemented with equimolar amounts of glutamate (+Glu; 55 mg · kg(-1) · d(-1); n = 5), leucine (+Leu; 49 mg · kg(-1) · d(-1); n = 5), lysine (+Lys; 55 mg · kg(-1) · d(-1); n = 5), or phenylalanine (+Phe; 62 mg · kg(-1) · d(-1); n = 6). The plasma concentrations of the supplemented amino acid in horses receiving the +Leu, +Lys, and +Phe diets were 58, 53, and 36% greater, respectively, than for the control treatment (P < 0.05). Isotopic plateau was attained in blood [1-(13)C] phenylalanine and breath (13)CO(2) enrichments by 60 and 270 min, respectively. Phenylalanine flux (+20%) and oxidation (+110%) were greater (P < 0.05) in horses receiving the +Phe treatment than in those fed the control diet. There was no effect of treatment diet on nonoxidative phenylalanine disposal or phenylalanine release from protein breakdown. The developed methods are a valuable way to study protein metabolism and assess dietary amino acid adequacy in horses and will provide a useful tool for studying amino acid requirements in the future.

Effect of feeding a high-protein diet following an 18-hour period of feed withholding on mammalian target of rapamycin-dependent signaling in skeletal muscle of mature horses.

OBJECTIVE: To determine the effect of refeeding following an 18-hour period of feed withholding on the phosphorylation of translation initiation factors in the skeletal muscle of mature horses. ANIMALS: 8 adult horses. PROCEDURES: Following an 18-hour period of feed withholding, horses either continued to have feed withheld (postabsorptive state) or were fed 2 g/kg of a high-protein feed (33% crude protein) at time 0 and 30 minutes (postprandial state). Blood samples were taken throughout the experimental period. At 90 minutes, a biopsy specimen was taken from the middle gluteal muscle to measure the phosphorylation of translation initiation factors and tissue amino acid concentrations. Plasma glucose, insulin, and amino acid concentrations were also measured. RESULTS: Horses in the postprandial state had significantly higher plasma insulin, glucose, and amino acid concentrations than did those in the postabsorptive state at the time of biopsy. Refeeding significantly increased the phosphorylation state of riboprotein S6 and eukaryotic initiation factor 4E binding protein 1. CONCLUSIONS AND CLINICAL RELEVANCE: In mature horses, feeding resulted in increased mammalian target of rapamycin signaling and the mechanism appeared to be independent of an increase in Akt phosphorylation at Ser47³. Results indicate that adult horses may be able to increase rates of muscle protein synthesis in response to feeding and that dietary amino acids appear to be the main mediators of this effect.

Glucose and insulin dynamics associated with continuous rate infusion of dextrose solution or dextrose solution and insulin in healthy and endotoxin-exposed horses.

OBJECTIVE: To investigate the effects of a continuous rate infusion (CRI) of dextrose solution or dextrose solution and insulin on glucose and insulin concentrations in healthy and endotoxin-exposed horses. ANIMALS: 9 adult mares. PROCEDURES: During phase 1, treatments consisted of saline (0.9% NaCl) solution (control group; n = 4) or 20% dextrose solution (group 1; 4) administered IV as a 360-minute CRI. During phase 2, treatments consisted of 360-minute CRIs of 20% dextrose solution and insulin administered simultaneously at 367.6 mg/kg/h (30 kcal/kg/d) and 0.07 U/kg/h, respectively, in healthy horses (group 2; n = 4) or horses administered 35 ng of lipopolysaccharide/kg, IV, 24 hours before starting the dextrose solution and insulin CRIs (group 3; 4). A balanced crossover study design was used in both phases. Blood samples were collected for measurement of plasma glucose and insulin concentrations. RESULTS: Infusion of dextrose solution alone resulted in hyperglycemia for most of the 360-minute CRI. Insulin concentration increased significantly in group 1, compared with that in the control group. Mean insulin concentration of group 2 was significantly higher throughout most of the infusion period, compared with concentrations of the control group and group 1. Mean glucose concentration did not differ significantly between groups 2 and 3. CONCLUSIONS AND CLINICAL RELEVANCE: Insulin infusion at a rate of 0.07 U/kg/h was found to be effective for the prevention of hyperglycemia when administered concurrently with dextrose solution. This rate was considered to be safe because horses did not become hypoglycemic during infusions of dextrose solution.

Effects of pretreatment with dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics in horses.

OBJECTIVE: To investigate the effects of dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics. ANIMALS: 24 horses. PROCEDURES: Horses were randomly allocated to 3 treatment groups and received 48 mg of levothyroxine mixed with 200 g of oats, 20 mg of dexamethasone plus oats, or oats alone (control) for 15 days, followed by IV infusion of lipopolysaccharide (20 ng/kg) while individually housed in stalls. Frequently sampled IV glucose tolerance tests were performed prior to pretreatment, after pretreatment, and 20 hours after lipopolysaccharide administration. Area under the curve for plasma glucose and serum insulin concentrations was calculated, and minimal model analyses were performed. RESULTS: Significant treatment-by-time effects were detected for insulin sensitivity (SI) and area under the curve for glucose and insulin in the 15-day pretreatment period. Insulin sensitivity significantly decreased over time in all treatment groups, with the largest decrease detected in the dexamethasone group. Administration of lipopolysaccharide further decreased mean SI by 71% and 63% in the dexamethasone and control groups, respectively, but did not affect horses in the levothyroxine group. Mean SI was the lowest in the dexamethasone group, but percentage reduction was the same for dexamethasone and control groups. CONCLUSIONS AND CLINICAL RELEVANCE: Insulin sensitivity decreased during the pretreatment period in all 3 groups, indicating that hospitalization affected glucose and insulin dynamics. Dexamethasone significantly lowered SI, and endotoxemia further exacerbated insulin resistance. In contrast, there was no additional effect of endotoxemia on SI in horses pretreated with levothyroxine, suggesting that this treatment prevented endotoxemia-induced insulin resistance.

Effects of exercise training on adiposity, insulin sensitivity, and plasma hormone and lipid concentrations in overweight or obese, insulin-resistant horses.

OBJECTIVE: To determine effects of exercise training without dietary restriction on adiposity, basal hormone and lipid concentrations and glucose and insulin dynamics in overweight or obese, insulin-resistant horses. ANIMALS: 12 overweight or obese (body condition score > or = 7), insulin-resistant (insulin sensitivity < or = 1.2 x 10(-4) L/min/mU) geldings. PROCEDURES: 4 horses remained sedentary, and 8 horses were exercised for 4 weeks at low intensity and 4 weeks at higher intensity, followed by 2 weeks of detraining. Prior to and after each training period, frequently sampled IV glucose tolerance tests with minimal model analysis were performed and baseline plasma insulin, glucose, triglycerides, non-esterified fatty acids, and leptin concentrations were analyzed. Adiposity was assessed by use of morphometrics, ultrasonic subcutaneous fat thickness, and estimation of fat mass from total body water (deuterium dilution method). RESULTS: Body weight and fat mass decreased by 4% (mean +/- SD, 20 +/- 8 kg) and 34% (32 +/- 9 kg), respectively, compared with pre-exercise values, with similar losses during low- and higher-intensity training. There was no effect of exercise training on subcutaneous fat thickness, plasma hormone and lipid concentrations, or minimal model parameters of glucose and insulin dynamics. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that moderate exercise training without concurrent dietary restriction does not mitigate insulin resistance in overweight or obese horses. A more pronounced reduction in adiposity or higher volume or intensity of exercise may be necessary for improvement in insulin sensitivity in such horses.

Current concepts on the pathophysiology of pasture-associated laminitis.

Epidemiologic studies indicate that most laminitis cases occur in horses and ponies kept at pasture, hence the term 'pasture-associated laminitis'. Clinical cases of laminitis most often occur under conditions that favor accumulation of rapidly fermentable nonstructural carbohydrates (fructans, simple sugars, or starches) in pasture, and animals with an equine metabolic syndrome (EMS) phenotype (insulin resistance, abnormal insulin dynamics, +/- obesity) seem to be at highest risk for developing the condition. Although the mechanisms linking consumption of pasture forage with development of lamellar failure have not been fully elucidated, a systemic inflammatory response that accompanies hindgut carbohydrate overload likely initiates lamellar inflammatory events (including infiltration and activation of leukocytes) that contribute to destruction of lamellar epithelium and extracellular matrix. This article reviews current knowledge on the epidemiology and risk factors for pasture-associated laminitis, including the role of forage carbohydrates and metabolic/endocrine predispositions, and also discusses the pathophysiology of this condition.

Fluid and electrolyte supplementation after prolonged moderate-intensity exercise enhances muscle glycogen resynthesis in Standardbred horses.

We hypothesized that postexercise rehydration using a hypotonic electrolyte solution will increase the rate of recovery of whole body hydration, and that this is associated with increased muscle glycogen and electrolyte recovery in horses. Gluteus medius biopsies and jugular venous blood were sampled from six exercise-conditioned Standardbreds on two separate occasions, at rest and for 24 h following a competitive exercise test (CET) designed to simulate the speed and endurance test of a 3-day event. After the CETs, horses were given water ad libitum, and either a hypotonic commercial electrolyte solution (electrolyte) via nasogastric tube, followed by a typical hay/grain meal, or a hay/grain meal alone (control). The CET resulted in decreased total body water and muscle glycogen concentration of 8.4 +/- 0.3 liters and 22.6%, respectively, in the control treatment, and 8.2 +/- 0.4 liters and 21.9% in the electrolyte treatment. Electrolyte resulted in an enhanced rate of muscle glycogen resynthesis and faster restoration of hydration (as evidenced by faster recovery of plasma protein concentration, maintenance of plasma osmolality, and greater muscle intracellular fluid volume) during the recovery period compared with control. There were no differences in muscle Na, K, Cl, or Mg contents between the two treatments. It is concluded that oral administration of a hypotonic electrolyte solution after prolonged moderate-intensity exercise enhanced the rate of muscle glycogen resynthesis during the recovery period compared with control. It is speculated that postexercise dehydration may be one key contributor to the slow muscle glycogen replenishment in horses.

Oral acetate supplementation after prolonged moderate intensity exercise enhances early muscle glycogen resynthesis in horses.

Oral acetate supplementation enhances glycogen synthesis in some mammals. However, while acetate is a significant energy source for skeletal muscle at rest in horses, its effects on glycogen resynthesis are unknown. We hypothesized that administration of an oral sodium acetate-acetic acid solution with a typical grain and hay meal after glycogen-depleting exercise would result in a rapid appearance of acetate in blood with rapid uptake by skeletal muscle. It was further hypothesized that acetate taken up by muscle would be converted to acetyl CoA (and acetylcarnitine), which would be metabolized to CO2 and water via the tricarboxylic acid cycle, generating ATP within the mitochondria and thereby allowing glucose taken up by muscle to be preferentially incorporated into glycogen. Gluteus medius biopsies and jugular venous blood were sampled from nine exercise-conditioned horses on two separate occasions, at rest and for 24 h following a competition exercise test (CET) designed to simulate the speed and endurance test of a 3 day event. After the CETs, horses were allowed water ad libitum and either 8 l of a hypertonic sodium acetate-acetic acid solution via nasogastric gavage followed by a typical hay-grain meal (acetate treatment) or a hay-grain meal alone (control treatment). The CET significantly decreased muscle glycogen concentration by 21 and 17% in the acetate and control treatments, respectively. Acetate supplementation resulted in a rapid and sustained increase in plasma [acetate]. Skeletal muscle [acetyl CoA] and [acetylcarnitine] were increased at 4 h of recovery in the acetate treatment, suggesting substantial tissue extraction of the supplemented acetate. Acetate supplementation also resulted in an enhanced rate of muscle glycogen resynthesis during the initial 4 h of the recovery period compared with the control treatment; however, by 24 h of recovery there was no difference in glycogen replenishment between trials. It is concluded that oral acetate could be an alternative energy source in the horse.

Apparent adiposity assessed by standardised scoring systems and morphometric measurements in horses and ponies.

This study described a scoring system for the assessment of apparent neck adiposity and evaluated morphometric measurements for assessment of neck and overall adiposity. Twenty-one barren Thoroughbred mares, 13 Arabian geldings and 75 Welsh, Dartmoor, or crossbred pony mares, were clinically examined and blood samples analysed for insulin, glucose, leptin, and triglycerides. Bodyweight (BW), height, length, girth and abdominal circumferences, neck length, neck crest height and neck circumference were measured, and body condition scores (BCS) and cresty neck scores (CNS) were rated. Girth:height ratio had the strongest associations with BCS (r(s)=0.64, P<0.001 in horses; r(s)=0.83, P<0.001 in ponies) and blood variables, such as leptin (r(s)=0.39, P=0.024 in horses; r(s)=0.68, P<0.001 in ponies). Crest height and neck circumference:height ratio had the strongest association with CNS (r(s)>0.50, P<0.01) and blood variables, such as insulin (r(s)0.40, P<0.05). Cresty neck score was useful in the assessment of neck crest adiposity and had physiological relevance, as demonstrated by associations with blood variables. Girth:height was the most suitable morphometric for assessment of overall adiposity, and either crest height or neck circumference:height was a suitable morphometric for assessment of apparent neck adiposity.

Effects of diet-induced weight gain on insulin sensitivity and plasma hormone and lipid concentrations in horses.

OBJECTIVE: To determine the effects of diet-induced weight gain on glucose and insulin dynamics and plasma hormone and lipid concentrations in horses. ANIMALS: 13 adult geldings. PROCEDURES: Horses were fed 200% of their digestible energy requirements for maintenance for 16 weeks to induce weight gain. Frequently sampled IV glucose tolerance tests were performed before and after weight gain to evaluate glucose and insulin dynamics. Adiposity (assessed via condition scoring, morphometric measurements, and subcutaneous fat depth) and plasma concentrations of insulin, glucose, nonesterified fatty acids, triglycerides, and leptin were measured on a weekly or biweekly basis. RESULTS: Mean + or - SD body weight increased by 20% from 440 + or - 44 kg to 526 + or - 53 kg, and body condition score (scale, 1 to 9) increased from 6 + or - 1 to 8 + or - 1. Plasma glucose, triglyceride, and nonesterified fatty acid concentrations were similar before and after weight gain. Leptin and insulin concentrations increased with weight gain. Mean + or - SD insulin sensitivity decreased by 71 + or - 28%, accompanied by a 408 + or - 201% increase in acute insulin response to glucose, which resulted in similar disposition index before and after weight gain. CONCLUSIONS AND CLINICAL RELEVANCE: Diet-induced weight gain in horses occurred concurrently with decreased insulin sensitivity that was effectively compensated for by an increase in insulin secretory response. Obesity resulted in hyperinsulinemia and hyperleptinemia, compared with baseline values, but no changes in lipid concentrations were apparent. Preventing obesity is a potential strategy to help avoid insulin resistance, hyperinsulinemia, and hyperleptinemia in horses.

Pasture-associated laminitis.

Laminitis is a painful and debilitating condition of horses and ponies that has major economic and welfare implications. Anecdotal observations and the results of survey studies have indicated that most laminitis cases occur in horses and ponies kept at pasture (hence, the term pasture-associated laminitis). Risk for development of pasture-associated laminitis represents a dynamic interaction between animal predisposing factors (an insulin-resistant phenotype commonly termed equine metabolic syndrome) and environmental conditions, particularly the nonstructural carbohydrate (simple sugars, starches, and fructans) content of pasture forage. Countermeasures for avoidance of pasture-associated laminitis involve (1) mitigation of metabolic predisposition (insulin resistance and obesity) in high-risk horses and ponies and (2) dietary and pasture grazing management strategies that minimize exposure to the dietary conditions known to trigger laminitis in susceptible animals.

Primer on dietary carbohydrates and utility of the glycemic index in equine nutrition.

The feeding of "low carbohydrate" or "low glycemic" diets has been recommended for management of horses with metabolic and endocrine disorders in which insulin resistance is a component. A "low carbohydrate" diet is a misnomer, however, because horses require that a significant proportion of their daily ration comprises structural carbohydrates (fiber/forage) to maintain gut health and mental wellbeing. This article provides a detailed description of the different carbohydrates in equine feeds. It also reviews the terminology used to describe glucose and insulin responses to the ingestion of carbohydrates, in particular the concept of the glycemic index. Some of the factors that influence glycemic index in humans and the glycemic response to a meal in horses are also discussed.

Dietary management of obesity and insulin resistance: countering risk for laminitis.

Insulin resistance (IR) and hyperinsulinemia increase risk for development of laminitis in horses and ponies. Obesity also has been associated with heightened risk for laminitis, likely by means of development of IR. Dietary factors, particularly the nonstructural carbohydrate (NSC) load, modulate risk for laminitis in these animals by means of exacerbation of IR or gastrointestinal disturbances that trigger the condition. Specific dietary management strategies to lessen risk for laminitis include caloric restriction to promote weight loss and improve insulin sensitivity in obese animals and strict control of dietary NSCs, with elimination of grains and sweet feeds from the ration and restricted access to pastures that may be rich in NSCs. Medical treatment with levothyroxine or metformin may be indicated in animals that do not respond to conservative dietary management.

Feeding management of sick neonatal foals.

Nutritional support of the foal can be challenging because of the constant changes in nutritional requirements and dietary composition during the transition from neonate to weanling. Additional complexity arises because of dilemmas regarding the means and route of delivery of nutrition to the foal, and the possibility that metabolic dysfunction may impair the ability of the foal to use nutrients appropriately. This article provides practical information on enteral and parenteral nutritional support of sick neonatal foals. The potential benefits of a conservative, hypocaloric feeding strategy, particularly in the very sick patient, are also discussed.

Effects of dexamethasone administration on insulin resistance and components of insulin signaling and glucose metabolism in equine skeletal muscle.

OBJECTIVE: To determine the effects of dexamethasone treatment on selected components of insulin signaling and glucose metabolism in skeletal muscle obtained from horses before and after administration of a euglycemic-hyperinsulinemic clamp (EHC). ANIMALS: 6 adult Standardbreds. PROCEDURES: In a balanced crossover study, horses received either dexamethasone (0.08 mg/kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution, IV, for 21 days. A 2-hour EHC was administered for measurement of insulin sensitivity 1 day after treatment. Muscle biopsy specimens obtained before and after the EHC were analyzed for glucose transporter 4, protein kinase B (PKB), glycogen synthase kinase (GSK)-3alpha/beta protein abundance and phosphorylation state (PKB Ser(473) and GSK-3alpha/beta Ser(21/9)), glycogen synthase and hexokinase enzyme activities, and muscle glycogen concentration. RESULTS: Dexamethasone treatment resulted in resting hyperinsulinemia and a significant decrease (70%) in glucose infusion rate during the EHC. In the dexamethasone group, increased hexokinase activity, abrogation of the insulin-stimulated increase in glycogen synthase fractional velocity, and decreased phosphorylation of GSK-3alpha Ser(21) and GSK-3B Ser(9) were detected, but there was no effect of dexamethasone treatment on glucose transporter 4 content and glycogen concentration or on PKB abundance and phosphorylation state. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, 21 days of dexamethasone treatment resulted in substantial insulin resistance and impaired GSK-3 phosphorylation in skeletal muscle, which may have contributed to the decreased glycogen synthase activity seen after insulin stimulation.

Effects of an intravenous endotoxin challenge on glucose and insulin dynamics in horses.

OBJECTIVE: To evaluate the effects of endotoxin administered IV on glucose and insulin dynamics in horses. ANIMALS: 16 healthy adult mares. PROCEDURES: Each week of a 2-week randomized crossover study, each horse received an IV injection (duration, 30 minutes) of Escherichia coli O55:B5 lipopolysaccharide (LPS) in 60 mL of sterile saline (0.9% NaCl) solution (20 ng/kg) or sterile saline solution alone (control treatment). Frequently sampled IV glucose tolerance test procedures were performed at 24 hours before (baseline) and 24 and 48 hours after injection; glucose and insulin dynamics were assessed via minimal model analysis. RESULTS: 13 of 16 horses had a clinical response to LPS, which was characterized by mild colic and leukopenia. Before treatment, mean +/- SD insulin sensitivity was 2.9 +/- 1.9 x 10(4) L x min(1) x mU(1); this significantly decreased to 0.9 +/- 0.9 x 10(4) L x min(1) x mU(1) 24 hours after treatment (69% reduction) and was 1.5 +/- 0.9 x 10(4) L x min(1) x mU(1) 48 hours after treatment. At baseline, mean +/- SD acute insulin response to glucose was 520 +/- 196 mU x min x L(1); this significantly increased to 938 +/- 620 mU x min x L(1) (80% increase) and 755 +/- 400 mU x min x L(1) (45% increase) at 24 and 48 hours after LPS treatment, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with baseline values, insulin sensitivity was decreased for 24 hours after IV injection of LPS, and affected horses had a compensatory pancreatic response. These disturbances in glucose and insulin dynamics may contribute to development of laminitis in horses.

Effect of Endurance Conditioning on Insulin-mediated Glucose Clearance in Dogs.

INTRODUCTION: Physical activity has been shown to improve insulin sensitivity in subjects with insulin resistance, but the effect of athletic conditioning on subjects with normal insulin sensitivity has received less scrutiny. Because strenuous exercise can be limited by the availability of substrates, it is reasonable to hypothesize that conditioning would increase the capacity for muscle uptake of substrates like glucose and to the extent that improvement in this process would include upregulation of the portions of the glucose uptake pathway in muscle, this increased capacity would also be reflected in insulin sensitivity. Therefore, we tested the hypothesis that conditioning for endurance exercise would result in increased insulin sensitivity using elite racing sled dogs. METHODS: A frequent-sampled intravenous glucose tolerance test was performed on these dogs before and after a full 7-month season of conditioning in preparation for a 1600-km race. RESULTS: Compared with the results in unconditioned dogs, conditioned dogs rapidly cleared the intravenous glucose bolus through increases in both glucose mediated (7.6%·min ± 3.4%·min vs 3.0%·min ± 2.2%·min, P = 0.008) and insulin-mediated (36.3 ± 18.4 × 10 L·min·mU vs 11.5 ± 8.0 × 10 L·min·mU, P = 0.007) mechanisms. The more modest increase in serum insulin after the intravenous glucose bolus in conditioned dogs failed to suppress lipolysis and serum concentrations of nonesterified fatty acids remained constant in the conditioned dogs throughout the 4-h test. CONCLUSIONS: These results, in particular the increase in insulin-independent peripheral uptake of glucose, describe novel alterations in metabolism induced by athletic conditioning that arguably result in near-continuous provision of oxidizable substrates to peripheral muscle in support of sustained muscular work typical of these dogs.

Metabolic perturbations in Welsh Ponies with insulin dysregulation, obesity, and laminitis.

BACKGROUND: Metabolomics, the study of small-molecule metabolites, has increased understanding of human metabolic diseases, but has not been used to study equine metabolic syndrome (EMS). OBJECTIVES: (1) To examine the serum metabolome of Welsh Ponies with and without insulin dysregulation before and during an oral sugar test (OST). (2) To identify differences in metabolites in ponies with insulin dysregulation, obesity, or history of laminitis. ANIMALS: Twenty Welsh Ponies (mean ± SD; 13.8 ± 9.0 years) classified as non-insulin dysregulated [CON] (n = 10, insulin < 30 mU/L) or insulin dysregulated [ID] (n = 10, insulin > 60 mU/L) at 75 minutes after administration of Karo syrup, obese (n = 6) or nonobese (n = 14), and history of laminitis (n = 9) or no history of laminitis (n = 11). METHODS: Case-control study. Metabolomic analysis was performed on serum obtained at 0 minutes (baseline) and 75 minutes during the OST. Data were analyzed with multivariable mixed linear models with significance set at P ≤ .05. RESULTS: Metabolomic analysis of 646 metabolites (506 known) detected significant metabolite differences. At baseline, 55 metabolites (insulin response), 91 metabolites (obesity status), and 136 metabolites (laminitis history) were different. At 75 minutes, 51 metabolites (insulin response), 102 metabolites (obesity status), and 124 metabolites (laminitis history) were different. CONCLUSIONS AND CLINICAL IMPORTANCE: Use of metabolomics could have diagnostic utility for early detection of EMS and provide new knowledge regarding the pathophysiology of metabolic perturbations associated with this condition that might lead to improved clinical management.

Time course of insulin sensitivity and skeletal muscle glycogen synthase activity after a single bout of exercise in horses.

The time course of insulin sensitivity, skeletal muscle glycogen and GLUT4 content, and glycogen synthase (GS) activity after a single bout of intense exercise was examined in eight horses. On separate days, a euglycemic-hyperinsulinemic clamp (EHC) was undertaken at 0.5, 4, or 24 h after exercise or after 48 h of rest [control (Con)]. There was no increase in mean glucose infusion rate (GIR) with exercise (0.5-, 4-, and 24-h trials), and GIR was significantly decreased at 0.5 h postexercise (GIR: 8.6 +/- 2.7, 6.7 +/- 2.0, 9.0 +/- 2.0, and 10.6 +/- 2.2 mg.kg(-1).min(-1) for Con and at 0.5, 4, and 24 h, respectively). Before each EHC, muscle glycogen content (mmol glucosyl units/kg dry muscle) was higher (P < 0.05) for Con (565 +/- 102) than for other treatments (317 +/- 84, 362 +/- 79, and 382 +/- 74 for 0.5, 4, and 24 h, respectively) and muscle GLUT4 content was unchanged. Pre-EHC active-to-total GS activity ratio was higher (P < 0.05) at 0.5, 4, and 24 h after exercise than in Con. Post-EHC active GS and GS activity ratio were higher (P < 0.05) in Con and at 24 h. There was a significant inverse correlation (r = -0.43, P = 0.02) between glycogen content and GS activity ratio but no relationship between GS activity and GIR. The lack of increase in insulin sensitivity, determined by EHC, after exercise that resulted in a significant reduction in muscle glycogen content is consistent with the slow rate of muscle glycogen resynthesis observed in equine studies.

Acute renal failure in horses.

Acute renal failure (ARF) in horses is usually prerenal or renal in origin and is most often caused by hemodynamic or nephrotoxic insults. The clinical management of patients that have ARF is largely supportive, including correction of fluid deficits and electrolyte and acid-base disturbances and treatment and reversal of the underlying cause. Use of dopamine and mannitol to promote renal blood flow and urine output is no longer recommended.