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  • Author or Editor: Raymond J. Geor x
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Abstract

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.

Full access
in American Journal of Veterinary Research

Abstract

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 × 10−4 L·min−1·mU−1; this significantly decreased to 0.9 ± 0.9 × 10−4 L·min−1·mU−1 24 hours after treatment (69% reduction) and was 1.5 ± 0.9 × 10−4 L·min−1·mU−1 48 hours after treatment. At baseline, mean ± SD acute insulin response to glucose was 520 ± 196 mU·min·L−1; this significantly increased to 938 ± 620 mU·min·L−1 (80% increase) and 755 ± 400 mU·min·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.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare effects of low and high intensity warm-up exercise on oxygen consumption (O2) and carbon dioxide production (CO2 ) in horses. Animals—6 moderately conditioned adult Standardbreds.

Procedures—Horses ran for 2 minutes at 115% of maximum oxygen consumption (O2max), 5 minutes after each of the following periods: no warm-up (NoWU); 10 minutes at 50% of O2max (LoWU); or 7 minutes at 50% O2max followed by 45-second intervals at 80, 90, and 100% O2max (HiWU). Oxygen consumption and CO2 were measured during exercise, and kinetics of O2 and CO2 were calculated. Accumulated O2 deficit was also calculated.

Results—For both warm-up trials, the time constant for the rapid exponential increase in O2 was 30% lower than for NoWU. Similarly, the rate of increase in CO2 was 23% faster in LoWU and HiWU than in NoWU. Peak values for O2 achieved during the highspeed test were not significantly different among trials (LoWU, 150.2 ± 3.2 ml/kg/min; HiWU, 151.2 ± 4.2 ml/kg/min; NoWU, 145.1 ± 4.1 ml/kg/min). However, accumulated O2 deficit (ml of O2 equivalents/kg) was significantly lower during LoWU (65.3 ± 5.1) and HiWU (63.4 ± 3.9) than during NoWU (82.1 ± 7.3).

Conclusions and Clinical Relevance—Both the lowand high-intensity warm-up, completed 5 minutes before the start of high-intensity exercise, accelerated the kinetics of O2 and CO2 and decreased accumulated O2 deficit during 2 minutes of intense exertion in horses that were moderately conditioned. (Am J Vet Res 2000;61:638–645)

Full access
in American Journal of Veterinary Research

Abstract

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.

Full access
in American Journal of Veterinary Research

Abstract

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.

Full access
in American Journal of Veterinary Research

Abstract

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.

Full access
in American Journal of Veterinary Research

Abstract

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 ± SD body weight increased by 20% from 440 ± 44 kg to 526 ± 53 kg, and body condition score (scale, 1 to 9) increased from 6 ± 1to8 ± 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 ± SD insulin sensitivity decreased by 71 ± 28%, accompanied by a 408 ± 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.

Full access
in American Journal of Veterinary Research

Abstract

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 ≥ 7), insulin-resistant (insulin sensitivity ≤ 1.2 × 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.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To characterize the effects of pregnancy on insulin sensitivity (SI) and glucose dynamics in pasture-maintained mares fed supplemental feeds of differing energy composition.

Animals—Pregnant (n = 22) and nonpregnant (10) healthy Thoroughbred mares.

Procedures—Pregnant and nonpregnant mares underwent frequently sampled intravenous glucose tolerance tests at 2 times (period 1, 25 to 31 weeks of gestation; period 2, 47 weeks of gestation). Following period 1 measurements, mares were provided a high-starch (HS; 39% starch) or high-fat and -fiber (14% fat and 70% fiber) supplemental feed. From a subset of mares (n = 12), blood samples were collected hourly for 24 hours to assess glycemic and insulinemic response to feeding while pastured. The minimal model of glucose and insulin dynamics was used to estimate SI, glucose effectiveness, and acute insulin response to glucose from tolerance testing data.

Results—Pregnant mares during period 1 had a lower SI and glucose effectiveness and higher acute insulin response to glucose than did nonpregnant mares. The SI value decreased in nonpregnant but not pregnant mares from periods 1 to 2. Pregnant mares fed HS feed had a greater glycemic and insulinemic response to feeding than did any other group.

Conclusions and Clinical Relevance—Pregnant mares had slower glucose clearance and greater insulin secretion at 28 weeks of gestation than did nonpregnant mares. Glucose and insulin responses to meal feeding, particularly with HS feed, were greater in pregnant mares, indicating that pregnancy enhanced the postprandial glycemic and insulinemic effects of starch-rich feed supplements.

Full access
in American Journal of Veterinary Research