Objective—To ascertain whether laminitis can be induced via administration of oligofructose (OF) at doses of 5.0 and 7.5 g/kg in horses and to assess glucose and insulin dynamics before and after treatment.
Animals—19 adult horses.
Procedures—Horses were fed OF (1.0 g/kg) mixed with oats for 6 days. Oligofructose at doses of 5.0 and 7.5 g/kg was then mixed with 4 L of water and administered (0 hours) to 8 (group A) and 4 (group B) horses, respectively, via nasogastric intubation; 8 horses received water alone. One horse in group A that did not develop laminitis was subsequently treated again and included in group B. Before and at intervals after treatment, resting plasma glucose and serum insulin concentrations were measured and frequently sampled IV glucose tolerance tests were performed. Area under the glucose curve (AUCg) and area under the insulin curve (AUCi) were calculated, and minimal model analyses were performed.
Results—3 of 8 horses in group A and all 4 horses in group B developed laminitis. Significant treatment-time effects were detected for resting plasma glucose concentrations and AUCg. Among horses in group A, mean AUCg values at 24 and 48 hours were 34% and 32% higher, respectively, than the mean value at 24 hours. Treatment groups did not differ significantly with respect to resting serum insulin concentration, AUCi, or minimal model analysis results.
Conclusions and Clinical Relevance—In horses, laminitis can be induced and glucose dynamics altered via nasogastric administration of 5.0 g of OF/kg. An alteration in insulin dynamics was not detected following treatment with OF.
Objective—To evaluate the effect of a soy-based diet on general health and adrenocortical and thyroid gland function in dogs.
Animals—20 healthy privately owned adult dogs.
Procedures—In a randomized controlled clinical trial, dogs were fed a soy-based diet with high (HID; n = 10) or low (LID; 10) isoflavones content. General health of dogs, clinicopathologic variables, and serum concentrations of adrenal gland and thyroid gland hormones were assessed before treatment was initiated and up to 1 year later. Differences between groups with respect to changes in the values of variables after treatment were assessed by means of a Student t test (2 time points) and repeated-measures ANOVA (3 time points).
Results—No differences were detected between the 2 groups with respect to body condition and results of hematologic, serum biochemical, and urine analyses. Most serum concentrations of hormones did not change significantly after treatment, nor were they affected by diet. However, the mean change in serum concentration of total thyroxine was higher in the HID group (15.7 pmol/L) than that in the LID group (–1.9 pmol/L). The mean change in estradiol concentration after ACTH stimulation at 1 year after diets began was also higher in the HID group (19.0 pg/mL) than that in the LID group (–5.6 pg/mL).
Conclusions and Clinical Relevance—Phytoestrogens may influence endocrine function in dogs. Feeding soy to dogs on a long-term basis may influence results of studies in which endocrine function is evaluated, although larger studies are needed to confirm this supposition.
Objective—To compare the effects of IV administration of various doses of ovine corticotrophin–releasing hormone (oCRH) on plasma and saliva cortisol concentrations in healthy horses and determine whether an oCRH challenge test protocol is valid for use in adult horses.
Animals—24 healthy Warmblood horses.
Procedures—Each horse received oCRH in saline (0.9% NaCl) via IV administration at a dose of 0 (control treatment), 0.01, 0.1, or 1.0 Mg/kg (6 horses/group). Jugular blood and saliva samples were collected simultaneously 15 minutes before and immediately prior to injection (baseline); data from these samples were pooled to provide basal values. Subsequently, 14 postinjection blood and saliva samples were both collected within a 210-minute period. Cortisol concentrations in all samples were assessed via a solid-phase radioimmunoassay.
Results—All doses of oCRH induced significant increases from baseline in both plasma and salivary cortisol concentrations. Compared with the smaller doses of oCRH, the 1.0 Mg/kg dose of oCRH induced significantly greater plasma cortisol concentrations. A relationship (r = 0.518) between basal cortisol concentrations in plasma and saliva was detected.
Conclusions and Clinical Relevance—For use as a CRH challenge test in adult horses, a protocol involving IV administration of a dose of at least 0.01 Mg of oCRH/kg and postinjection collection of blood samples from 10 to 180 minutes and saliva samples from 20 to 50 minutes for assessment of plasma and saliva cortisol concentrations should be sufficient. Application of such a test might be helpful to detect states of chronic activation of the hypothalamo-pituitary-adrenocortical axis at the hypothalamic level.
Objective—To assess changes in serum concentrations of thyroid hormones associated with selenium deficiency myopathy in lambs.
Animals—35 lambs with selenium deficiency myopathy and 30 healthy lambs.
Procedures—Blood samples were collected via jugular venipuncture from lambs with selenium deficiency myopathy and healthy lambs. Activities of markers of selenium deficiency myopathy (erythrocyte glutathione peroxidase [GSH-Px] and plasma creatine kinase [CK]) and serum thyroid-stimulating hormone (TSH) and total thyroxine (tT4) and total triiodothyronine (tT3) concentrations were assessed; values in affected lambs were compared with those in healthy lambs. Correlations of erythrocyte GSH-Px and plasma CK activities with serum concentrations of TSH, tT4, and tT3 were investigated, and the tT3:tT4 concentration ratio was evaluated.
Results—Compared with findings in healthy lambs, erythrocyte GSH-Px activity, serum tT3 concentration, and tT3:tT4 concentration ratio were significantly decreased and serum concentrations of tT4 and TSH and the activity of plasma CK were significantly increased in affected lambs. Analysis revealed a significant negative correlation in the affected group between erythrocyte GSH-Px activity and each of the following: plasma CK activity (r = −0.443), serum TSH concentration (r = −0.599), serum tT4 concentration (r = −0.577), and serum tT3 concentration (r = −0.621).
Conclusions and Clinical Relevance—Results suggested that notable changes in circulating amounts of thyroid hormones develop in association with selenium deficiency in lambs. Such alterations in thyroid hormone metabolism may be involved in the high incidence of disorders, such as stillbirths and neonatal deaths, in selenium-deficient flocks.
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)-3α/β protein abundance and phosphorylation state (PKB Ser473 and GSK-3α/β Ser21/9), 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-3α Ser21 and GSK-3B Ser9 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.
Objective—To determine effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses.
Animals—6 adult Standardbreds.
Procedures—In a balanced crossover study, horses received dexamethasone (0.08 mg/ kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution (control treatment) during a 21-day period. Horses underwent a 3-hour frequently sampled IV glucose tolerance test (FSIGT) 2 days after treatment. Minimal model analysis of glucose and insulin data from FSIGTs were used to estimate insulin sensitivity (Si), glucose effectiveness (Sg), acute insulin response to glucose (AIRg), and disposition index. Proxies for Si (reciprocal of the inverse square of basal insulin concentration [RISQI]) and beta-cell responsiveness (modified insulin-to-glucose ratio [MIRG]) were calculated from basal plasma glucose and serum insulin concentrations.
Results—Mean serum insulin concentration was significantly higher in dexamethasone-treated horses than control horses on days 7, 14, and 21. Similarly, mean plasma glucose concentration was higher in dexamethasone-treated horses on days 7, 14, and 21; this value differed significantly on day 14 but not on days 7 or 21. Minimal model analysis of FSIGT data revealed a significant decrease in Si and a significant increase in AIRg after dexamethasone treatment, with no change in Sg or disposition index. Mean RISQI was significantly lower, whereas MIRG was higher, in dexamethasone-treated horses than control horses on days 7, 14, and 21.
Conclusions and Clinical Relevance—The study revealed marked insulin resistance in healthy horses after 21 days of dexamethasone administration. Because insulin resistance has been associated with a predisposition to laminitis, a glucocorticoid-induced decrease in insulin sensitivity may increase risk for development of laminitis in some horses and ponies.
Objective—To determine effects of experimentally induced hypercalcemia on serum concentrations and urinary excretion of electrolytes, especially ionized magnesium (iMg), in healthy horses.
Animals—21 clinically normal mares.
Procedures—Horses were assigned to 5 experimental protocols (1, hypercalcemia induced with calcium gluconate; 2, hypercalcemia induced with calcium chloride; 3, infusion with dextrose solution; 4, infusion with sodium gluconate; and 5, infusion with saline [0.9% NaCl] solution). Hypercalcemia was induced for 2 hours. Dextrose, sodium gluconate, and saline solution were infused for 2 hours. Blood samples were collected to measure serum concentrations of electrolytes, creatinine, parathyroid hormone, and insulin. Urine samples were collected to determine the fractional excretion of ionized calcium (iCa), iMg, sodium, phosphate, potassium, and chloride.
Results—Hypercalcemia induced by administration of calcium gluconate or calcium chloride decreased serum iMg, potassium, and parathyroid hormone concentrations; increased phosphate concentration; and had no effect on sodium, chloride, and insulin concentrations. Hypercalcemia increased urinary excretion of iCa, iMg, sodium, phosphate, potassium, and chloride; increased urine output; and decreased urine osmolality and specific gravity. Dextrose administration increased serum insulin; decreased iMg, potassium, and phosphate concentrations; and decreased urinary excretion of iMg. Sodium gluconate increased the excretion of iCa, sodium, and potassium.
Conclusions and Clinical Relevance—Hypercalcemia resulted in hypomagnesemia, hypokalemia, and hyperphosphatemia; increased urinary excretion of calcium, magnesium, potassium, sodium, phosphate, and chloride; and induced diuresis. This study has clinical implications because hypercalcemia and excessive administration of calcium have the potential to increase urinary excretion of electrolytes, especially iMg, and induce volume depletion.
Objective—To assess serum concentrations of adiponectin and characterize adiponectin protein complexes in healthy dogs.
Animals—11 healthy dogs.
Procedures—Sera collected from 10 dogs were evaluated via velocity sedimentation and ultracentrifugation, SDS-PAGE, western immunoblotting, and radioimmunoassay. Visceral adipose tissue (approx 90 g) was collected from the falciform ligament of a healthy dog undergoing elective ovariohysterectomy, and adiponectin gene expression was assessed via a real-time PCR procedure.
Results—Adiponectin gene expression was detected in visceral adipose tissue. Serum adiponectin concentrations ranged from 0.85 to 1.5 μg/mL (mean concentration, 1.22 μg/mL). In canine serum, adiponectin was present as a multimer, consisting of a low–molecular-weight complex (180 kd); as 3 (180-, 90-, and 60-kd) complexes under denaturing conditions; as 2 (90- and 60-kd) complexes under reducing conditions; and as a dimer, a monomer, and globular head region (60, 30, and 28 kd, respectively) under reducing-denaturing conditions. It is likely that adiponectin also circulates as a high–molecular-weight (360- to 540-kd) complex in canine serum, but resolution of this complex was not possible via SDS-PAGE.
Conclusions and Clinical Relevance—After exposure to identical experimental conditions, adiponectin protein complexes in canine serum were similar to those detected in human and rodent sera. Circulating adiponectin concentrations in canine serum were slightly lower than concentrations in human serum. Adiponectin gene expression was identified in canine visceral adipose tissue. Results suggest that adiponectin could be used as an early clinical marker for metabolic derangements, including obesity, insulin resistance, and diabetes mellitus in dogs.
Objective—To evaluate postprandial changes in the leptin concentration of CSF in dogs during development of obesity.
Animals—4 male Beagles.
Procedures—Weight gain was induced and assessments were made when the dogs were in thin, optimal, and obese body conditions (BCs). The fat area at the level of the L3 vertebra was measured via computed tomography to assess the degree of obesity. Dogs were evaluated in fed and unfed states. Dogs in the fed state received food at 9 AM. Blood and CSF samples were collected at 8 AM, 4 PM, and 10 PM.
Results—Baseline CSF leptin concentrations in the thin, optimal, and obese dogs were 24.3 ± 2.7 pg/mL, 86.1 ± 14.7 pg/mL, and 116.2 ± 47.3 pg/mL, respectively. In the thin BC, CSF leptin concentration transiently increased at 4 PM. In the optimal BC, baseline CSF leptin concentration was maintained until 10 PM. In the obese BC, CSF leptin concentration increased from baseline value at 4 PM and 10 PM. Correlation between CSF leptin concentration and fat area was good at all time points. There was a significant negative correlation between the CSF leptin concentration–to–serum leptin concentration ratio and fat area at 4 PM; this correlation was not significant at 8 AM and 10 PM.
Conclusions and Clinical Relevance—Decreased transport of leptin at the blood-brain barrier may be 1 mechanism of leptin resistance in dogs. However, leptin resistance at the blood-brain barrier may not be important in development of obesity in dogs.
Objective—To investigate the physiologic endocrine effects of food intake and food withholding via measurement of the circulating concentrations of acylated ghrelin, growth hormone (GH), insulin–like growth factor-I (IGF-I), glucose, and insulin when food was administered at the usual time, after 1 day's withholding, after 3 days' withholding and after refeeding the next day in healthy Beagles.
Animals—9 healthy Beagles.
Procedures—Blood samples were collected from 8:30 AM to 5 PM from Beagles when food was administered as usual at 10 AM, after 1 day's withholding, after 3 days' withholding, and after refeeding at 10 AM the next day.
Results—Overall mean plasma ghrelin concentrations were significantly lower when food was administered than after food withholding. Overall mean plasma GH and IGF-I concentrations did not differ significantly among the 4 periods. Circulating overall mean glucose and insulin concentrations were significantly higher after refeeding, compared with the 3 other periods.
Conclusions and Clinical Relevance—In dogs, food withholding and food intake were associated with higher and lower circulating ghrelin concentrations, respectively, suggesting that, in dogs, ghrelin participates in the control of feeding behavior and energy homeostasis. Changes in plasma ghrelin concentrations were not associated with similar changes in plasma GH concentrations, whereas insulin and glucose concentrations appeared to change reciprocally with the ghrelin concentrations.