Effects of a supplement containing chromium and magnesium on morphometric measurements, resting glucose, insulin concentrations and insulin sensitivity in laminitic obese horses

Reasons for performing study: Obesity and insulin resistance are risk factors for laminitis in equids and supplements containing chromium and magnesium might improve insulin sensitivity. Hypothesis: A supplement containing chromium, magnesium and other nutraceuticals would alter morphometric measurements, blood variables, and insulin sensitivity in laminitic obese horses. Methods: Twelve previously laminitic obese (body condition score ≥ 7/9) horses were randomly allocated to treatment (n = 6) and control (n = 6) groups and 2 obese horses with clinical laminitis were included in the treatment group. Treated animals received 56 g supplement with 0.25 kg oats once daily for 16 weeks. The supplement contained chromium (5 mg/day as yeast), magnesium (8.8 g/day as oxide/proteinate), and other nutraceuticals. Insulin‐modified frequently sampled i.v. glucose tolerance tests were performed with hay provided at 0, 8 and 16 weeks, and insulin sensitivity was estimated by minimal model analysis. Physical measurements were collected at the same points. Horses were not exercised. Results: Hyperinsulinaemia (>30 µu/ml) was detected in 12 of 14 horses prior to treatment. Glucose and insulin data from one mare with clinical laminitis were excluded because of persistent pain. Mean ± s.d. insulin sensitivity was 0.64 ± 0.62 × 10^?4 l/min/mu prior to treatment for the remaining 13 horses. Time and treatment × time effects were not significant for any of the variables examined, with the exception of resting insulin concentrations, which significantly increased over time (P = 0.018). Health status remained the same. Conclusions: The supplement containing chromium and magnesium evaluated in this study did not alter morphometric measurements, blood variables, resting insulin concentrations or insulin sensitivity in laminitic obese horses. Potential relevance: Additional research is required to determine the appropriate use of chromium and magnesium supplements in horses.     

Glucose and insulin response after intravenous and subcutaneous somatostatin administration in healthy horses

Equine metabolic syndrome (EMS) is prevalent in the equine population, and somatostatin analogs might be useful for diagnosis and/or treatment of EMS in horses. The purpose of this study was to evaluate the glucose and insulin responses to subcutaneous and intravenous administration of somatostatin. Six healthy research horses were included in this prospective study. An initial pilot study was performed to assess several different doses (10–22 µg/kg [4.5–10 µg/lb]) in two horses, then a final dosage of 22 µg/kg (10 µg/lb) was administered to six horses IV and SQ in a two‐period randomized cross‐over study performed over a 3‐month study period. Blood samples were collected for measurement of plasma insulin and glucose concentrations during a 24‐hr study period. Both IV and SQ somatostatin resulted in decreased insulin and increased glucose concentrations. SQ somatostatin resulted in a longer clinical effect, with return to baseline insulin occurring at 1.5 hr postadministration, versus 45 min for IV. Both IV and SQ administration of somatostatin to normal horses resulted in decreased insulin and increased glucose concentrations, likely due to suppression of insulin secretion by somatostatin. A more prolonged effect was seen following SQ administration as compared to IV administration, and no adverse effects were noted at varying doses. This study provides additional information regarding the effect of somatostatin administration on insulin and glucose concentrations in clinically healthy horses.     

Leucine markedly regulates pancreatic exocrine secretion in goats

Four goats (30.1 ± 1.3 kg) with common bile duct re‐entrant catheter and duodenal catheter were used to evaluate the effects of duodenal leucine infusion on pancreatic exocrine secretion and plasma parameters with two 4 × 4 Latin square design experiments. In the long‐term infusion experiment, goats were fed twice daily [700 g/day, dry matter (DM) basis] at 8:00 and 18:00 hours and were duodenally infused with 0, 3, 6, 9 g/day leucine for 14 days. Pancreatic juice and jugular blood samples were collected over 1‐h intervals for 6 h daily from d 11 to 14 days to encompass a 24‐h day. In the short‐term experiment, goats were infused leucine for 10 h continuously at the same infusion rate with Experiment 1 after feed deprivation for 24 h repeated every 10 days. Pancreatic juice and blood samples were collected at 0, 1, 2, 4, 6, 8 and 10 h of infusion. The results showed that the long‐term leucine infusion did not affect pancreatic juice secretion, protein output, trypsin and lipase secretion and plasma insulin concentration, but linearly increased α‐amylase secretion. No changes in pancreatic protein and lipase secretion were observed in the short‐term infusion. Pancreatic juice and α‐amylase secretion responded quadratically, with the greatest values observed in the 3 and 6 g/day leucine respectively. Trypsin secretion linearly decreased, while plasma insulin concentration increased linearly with increased leucine infusion. The results demonstrated that duodenal leucine infusion dose and time dependently regulated pancreatic enzyme secretion not associated with the change in plasma insulin concentration.     

Type 2 diabetes mellitus with pancreatic β cell dysfunction in 3 horses confirmed with minimal model analysis

Reasons for performing study: Type 2 diabetes mellitus (T2DM) is diagnosed rarely in equine practice although it may be under‐recognised. A greater awareness of the condition and therapeutic considerations would be to the benefit of such cases presenting in practice. More investigation into the pharmacological management of these cases is needed. Objectives: Three cases of diabetes mellitus were investigated using a specific test for insulin sensitivity and pancreatic β cell function in order to define accurately and characterise the existence of T2DM in all 3 subjects. Methods: The insulin‐modified frequently sampled i.v. glucose tolerance test was performed in each case and the data so obtained were subject to minimal model analysis of insulin‐glucose dynamics. Cases were then monitored following treatment using a combination of dietary modification, metformin, glibenclamide and pergolide. Results: Marked insulin resistance was identified in each case and, furthermore, severe pancreatic β cell dysfunction was present therefore classifying each case as end stage T2DM. Treatment was nevertheless associated with restoration of normoglycaemia in all cases. Conclusions: T2DM in horses may be more common than generally considered. In some cases individuals may respond to therapy aimed at restoring insulin sensitivity and pancreatic function. Drugs used in other species for the treatment of T2DM have not yet been adequately tested in horses. Potential relevance: T2DM should be considered as an important differential diagnosis in mature to elderly horses and ponies suffering from weight loss, polydipsia and polyuria. Clinicians should be encouraged to offer treatment and management advice when such cases are encountered.     

Effects of endotoxaemia and carbohydrate overload on glucose and insulin dynamics and the development of laminitis in horses

Reasons for performing study: Insulin resistance (IR) is a risk factor for pasture‐associated laminitis in equids and alimentary carbohydrate overload may trigger laminitis. Whether glucose metabolism responses to carbohydrate overload are more pronounced in insulin‐resistant horses requires further study. Hypothesis: Horses pretreated with endotoxin to alter insulin sensitivity differ significantly in their glucose and insulin responses to carbohydrate overload. Methods: Horses (n = 24) were divided into 3 groups. A lipopolysaccharide (LPS; n = 8) group that received endotoxin as an 8 h 7.5 ng/kg bwt/h i.v. continuous rate infusion, an oligofructose (OF; n = 8) group that received an infusion of saline followed by 5 g/kg bwt OF via nasogastric intubation, and a LPS/OF (n = 8) group that received LPS followed 16 h later by OF. Glucose and insulin dynamics were evaluated at ‐24 h and 48 h using the frequently sampled i.v. glucose tolerance test and minimal model analysis. Physical examinations and haematology were performed and the severity of laminitis assessed. Results: Horses receiving LPS developed leucopenia and both LPS and OF induced clinical signs consistent with systemic inflammation. Insulin sensitivity significantly decreased (P<0.001) over time, but responses did not differ significantly among groups. Time (P<0.001) and treatment × time (P = 0.038) effects were detected for the acute insulin response to glucose, with mean values significantly increasing in LPS and LPS/OF groups, but not the OF group. Five horses in the LPS/OF group developed clinical laminitis compared with 0 and 2 horses in the LPS and OF groups, respectively. Conclusions: Endotoxaemia and carbohydrate overload reduce insulin sensitivity in horses. Endotoxin pretreatment does not affect the alterations in glucose metabolism induced by carbohydrate overload. Potential relevance: Insulin sensitivity decreases after carbohydrate overload in horses, which may be relevant to the development of pasture‐associated laminitis.     

The diagnosis of equine insulin dysregulation

Insulin dysregulation is the hallmark of equine metabolic syndrome and has received attention because of its direct association with laminitis. In the absence of an adequate treatment for laminitis, a focus on prophylaxis is needed, making early detection of individuals at risk of developing laminitis one of the main challenges in equine endocrinology. Recent studies have shown that insulin dysregulation goes beyond tissue insulin resistance and it is now demonstrated that the equine enteroinsular axis plays a major role in insulin secretion and equine hyperinsulinaemia. In this review, we discuss the different tests currently available to diagnose insulin dysregulation in horses: the ones investigating tissue insulin resistance and those investigating the enteroinsular axis, detailing their goals, practicalities and limitations. This review supports the contention that the diagnosis of equine insulin dysregulation should now be based on the investigation of both tissue insulin resistance and the equine enteroinsular axis. Regardless of the tests used many factors of variation, such as breed, diet, fasting state or season, have been identified and could potentially confound the results of a specific test. Therefore, careful interpretation of the results of a given test in each individual situation is required to optimise the detection of horses at risk of laminitis.     

Effect of regular walking exercise on glucose tolerance and insulin response to i.v. glucose infusion in growing beef steers

The purpose of the present paper was to investigate the effect of regular walking exercise on glucose tolerance and insulin response to i.v. glucose infusion in growing beef steers. Four crossbred beef steers walked on a treadmill during a 6 week exercise period (1.2 km/h, 1 h/day and 5 days/week). The changes in plasma glucose and insulin levels following glucose infusion were analyzed immediately prior to (bodyweight: 260.4 ± 24.2 kg) and after (295.7 ± 30.1 kg) the exercise period. The basal levels of plasma glucose (86.4 vs. 82.0 mg/dL, P = 0.040) and insulin (24.5 vs. 14.3 μU/mL, P = 0.016) were significantly lower after the exercise period. Further, the increase in the levels of plasma glucose (420.4 vs. 280.8 mg/dL, P < 0.001) and insulin (94.5 vs. 73.1 μU/mL, P = 0.028) following the glucose infusion decreased after the exercise period. The area under the curve of plasma glucose (108.8 vs. 62.9 mg/dL per min, P < 0.001) and insulin (53.6 vs. 29.7 μU/mL per min, P = 0.018) indicated more rapid clearance of exogenous glucose and less insulin secretion for glucose clearance after the exercise period. These results suggest that regular exercise improves glucose tolerance, with lower insulin response to glucose infusion in growing steers, as observed in rodents and humans.     

Optimisation of the frequently sampled intravenous glucose tolerance test to reduce urinary glucose spilling in horses

Reasons for performing study: The frequently sampled i.v. glucose tolerance test (FSIGTT) is used to evaluate glucose and insulin dynamics in horses, but it has not been determined whether urinary glucose spilling (UGS) affects results. Hypothesis: UGS occurs in horses during the FSIGTT and this problem can be minimised by adjusting the dextrose and insulin dosages used. Methods: Six mature mares were included in this study. In the first phase, 6 FSIGTT procedures were performed in each horse to evaluate 6 different dextrose dosages. Six different insulin dosages were evaluated during the second phase of the study after administration of 300 mg/kg bwt dextrose. Area under the glucose (AUCg) and insulin (AUCi) curves were calculated and minimal model analyses performed. UGS was measured in the third and fourth phases of the study during the combined glucose insulin test and established FSIGTT. A new FSIGTT was developed and evaluated. Results: Positive linear effects of dextrose dosage on AUCg, AUCi and acute insulin response to glucose were detected, with AUCg reaching a plateau at doses 200 mg/kg bwt. Insulin dosage had an inverse linear effect on AUCg, but other values remained unaffected. UGS occurred during all 3 tests and was the highest for the established FSIGTT and the lowest for the new FSIGTT. The type of FSIGTT performed did not affect minimal model results. Conclusions: Results indicate that the dextrose dosage of 300 mg/kg bwt used in the established FSIGTT is too high. UGS can be reduced by lowering the dextrose dosage to 100 mg/kg bwt. Potential relevance: A new FSIGTT involving the administration of 100 mg/kg bwt dextrose followed by 20 mu/kg bwt insulin 20 min later is recommended for use in horses because this test provides adequate data for minimal model analysis while minimising UGS.     

Daily treatment of horses with equine somatotropin from 4 to 16 months of age.

Fourteen foals between 4 and 4.5 mo of age were used to determine the effects of 12 mo of daily treatment with equine somatotropin (eST) on growth, metabolic, and hormonal characteristics. The foals were paired by sex, type, and lineage, and one of each pair was administered eST daily at 20 microg/kg of BW. Body weights, body measurements, and assessments of glucose tolerance and feedback effects on endogenous somatotropin (ST) secretion were made routinely. Treatment with eST did not alter (P > 0.10) BW, height at withers, length of body, widths of chest and rump, heart girth, length of head, front or rear cannon lengths, front or rear cannon circumferences, gaskin circumference, or skin thickness, even though plasma IGF-I concentrations were doubled (P = 0.012). Glucose concentrations were higher (P = 0.03) in treated horses before glucose infusion; there was no difference (P > 0.10) in the glucose response to infusion. The insulin response to glucose infusion in the treated horses was generally higher (P = 0.0069) than in controls. Endogenous ST secretion in response to a ST secretagogue was reduced (P = 0.0001) in foals treated with eST in all months. The prolactin and thyroid-stimulating hormone responses to thyrotropin-releasing hormone on June 1 were not affected (P > 0.10) by treatment. In conclusion, daily treatment of growing horses with eST for 12 mo at the recommended dose altered the hormonal and metabolic characteristics known to be affected by ST but did not alter the growth characteristics of the animals.     

Glucose transport in the equine hoof

Reasons for performing study: Several conditions associated with laminitis in horses are also associated with insulin resistance, which represents the failure of glucose uptake via the insulin‐responsive glucose transport proteins in certain tissues. Glucose starvation is a possible mechanism of laminitis, but glucose uptake mechanisms in the hoof are not well understood. Objectives: To determine whether glucose uptake in equine lamellae is dependent on insulin, to characterise the glucose transport mechanism in lamellae from healthy horses and ponies, and to compare this with ponies with laminitis. Methods: Study 1 investigated the effects of insulin (300 µU/ml; acute and 24 h) and various concentrations of glucose up to 24 mmol/l, on 2‐deoxy‐D‐[2,6‐³H]glucose uptake in hoof lamellar explants in vitro. Study 2 measured the mRNA expression of GLUT1 and GLUT4 transport proteins by PCR analysis in coronary band and lamellar tissue from healthy horses and ponies, ponies with insulin‐induced laminitis, and ponies suffering from chronic laminitis as a result of equine Cushing's syndrome. Results: Glucose uptake was not affected by insulin. Furthermore, the relationship between glucose concentration and glucose uptake was consistent with an insulin‐independent glucose transport system. GLUT1 mRNA expression was strong in brain, coronary band and lamellar tissue, but was weak in skeletal muscle. Expression of GLUT4 mRNA was strong in skeletal muscle, but was either absent or barely detectable in coronary band and lamellar tissue. Conclusions: The results do not support a glucose deprivation model for laminitis, in which glucose uptake in the hoof is impaired by reduced insulin sensitivity. Hoof lamellae rely on a GLUT1‐mediated glucose transport system, and it is unlikely that GLUT4 proteins play a substantial role in this tissue. Potential relevance: Laminitis associated with insulin resistance is unlikely to be due to impaired glucose uptake and subsequent glucose deprivation in lamellae.     

Pharmacokinetics of acyclovir in adult horses

Objective: To determine the pharmacokinetics of acyclovir administered intravenously (IV) and orally to healthy adult horses. Design: Random cross‐over with an approximate 1‐week washout period between trials. Setting: University veterinary medical teaching hospital. Animals: Six healthy adult research herd horses. Interventions and main results: Acyclovir was administered IV (10 mg/kg in 1 L isotonic crystalloid solution over 60 minutes) and orally (20 mg/kg) to healthy adult horses. Plasma samples were obtained and acyclovir concentrations were determined by high‐pressure liquid chromatography. Peak concentration (mean±SD) for IV acyclovir was 13.74±5.88 μg/mL at the completion of the 1‐hour infusion. The half‐life of the distribution phase (α) was 0.16 hours while the half‐life of the elimination phase (β) was 9.6 hours. The steady‐state volume of distribution was 3.93±1.21 L/kg. We were unable to measure pharmacokinetics after PO acyclovir as plasma concentrations were below the lower limits of detection in all 6 horses. Conclusions: IV administration of acyclovir to healthy adult horses achieves concentrations within the sensitivity range described for equine herpes virus‐type 1. The oral bioavailability of acyclovir in horses is low and additional studies are required.     

Equine laminitis: Induced by 48 h hyperinsulinaemia in Standardbred horses

Reasons for performing study: Hyperinsulinaemia is known to induce laminitis experimentally in healthy ponies with no history of the condition. Horses are more insulin sensitive than ponies and whether prolonged hyperinsulinaemia and euglycaemia would have a similar laminitogenic effect requires study. Objectives: To determine if laminitis results when the prolonged euglycaemic hyperinsulinaemic clamp technique (p‐EHC) is applied to clinically normal Standardbred horses, and to monitor hoof wall temperature seeking an association between vascular activity and laminitis development. Methods: Eight young, clinically normal Standardbred horses were assigned into 4 pairs and within each pair, one was assigned randomly to either treatment (n = 4) or control (n = 4) groups. Treated horses received continuous infusions of insulin and glucose until clinical signs of laminitis developed, at which point the horses were subjected to euthanasia. Control horses received an equivalent volume of a balanced electrolyte infusion for the same period. Hoof wall surface temperature (HWST) was monitored continuously throughout the experimental period. Results: All horses in the treatment group were calculated to have normal insulin sensitivity. All treated horses, and none in the control group, developed laminitis (P = 0.01). Pronounced digital pulses were a feature of the treatment group, while insignificant digital pulses occurred in control horses. HWST was higher and less variable in treated horses once hyperinsulinaemia was established. Conclusions: Healthy Standardbred horses subjected to prolonged hyperinsulinaemia develop laminitis within 48 h, demonstrating that laminitis in horses can be triggered by insulin. Potential relevance: Insulin resistance and the associated hyperinsulinaemia place horses and ponies at risk of developing laminitis. This study demonstrates a need for prompt management of the persistent hyperinsulinaemia seen in some endocrinopathies.     

Effects of clopidogrel and aspirin on platelet aggregation, thromboxane production, and serotonin secretion in horses

Background: Critically ill horses are susceptible to thrombotic disease, which might be related to increased platelet reactivity and activation. Objectives: To compare the effect of oral clopidogrel and aspirin (ASA) on equine platelet function. Animals: Six healthy adult horses. Methods: Horses received clopidogrel (2 mg/kg PO q24h) or ASA (5 mg/kg PO q24h) for 5 days in a prospective randomized cross‐over design. Platelet aggregation responses to adenosine diphosphate (ADP) and collagen via optical aggregometry, and platelet secretion of serotonin (5HT) and production of thromboxane B₂ (TXB₂) by ELISA were evaluated. In horses receiving clopidogrel, high‐performance liquid chromatography analysis for clopidogrel and its carboxylic‐acid metabolite SR 26334 was performed. Results: SR 26334 was identified in all clopidogrel‐treated horses, although the parent compound was not detected. Clopidogrel resulted in decreases in ADP‐induced platelet aggregation persisting for 120 hours after the final dose. ADP‐induced platelet aggregation decreased from a baseline of 70.2 ± 14.7% to a minimum of 15.9 ± 7.7% 24 hours after the final dose (P < .001). Collagen‐induced aggregation decreased from a baseline of 93 ± 9.5% to a minimum of 70.8 ± 16.9% 48 hours after the final dose (P < .001). ASA did not decrease platelet aggregation with either agonist. ASA decreased serum TXB₂ from a baseline value of 1310 ± 1045 to 128 ± 64 pg/mL within 24 hours (P < .01). Conclusions and Clinical Importance: Clopidogrel effectively decreases ADP‐induced platelet aggregation in horses, and could have therapeutic applications for equine diseases associated with platelet activation.     

Effects of glucose and amino acids on ghrelin secretion in sheep

Two experiments were conducted to elucidate the effects of post‐ruminal administration of starch and casein (Exp. 1), plasma amino acids concentrations (Exp. 2), and plasma glucose and insulin concentrations (Exp. 2) on plasma ghrelin concentrations in sheep. In Exp. 1, plasma ghrelin concentrations were determined by four infusion treatments (water, cornstarch, casein and cornstarch plus casein) in four wethers. Abomasal infusion of casein increased plasma α‐amino N (AAN) concentrations. Infusion of starch or casein alone did not affect plasma ghrelin concentrations, but starch plus casein infusion increased plasma levels of ghrelin, glucose and AAN. In Exp 2, we investigated the effects of saline or amino acids on ghrelin secretion in four wethers. Two hours after the initiation of saline or amino acid infusion into the jugular vein, glucose was also continuously infused to investigate the effects of blood glucose and insulin by hyper‐glycemic clump on plasma ghrelin concentrations. Infusion of amino acids alone raised plasma levels of ghrelin, but the higher plasma glucose and insulin concentrations had no effect on plasma ghrelin concentrations. These results suggest that high plasma levels of amino acids can stimulate ghrelin secretion, but glucose and insulin do not affect ghrelin secretion in sheep.     

Growth hormone secretion and pancreatic function following somatostatin infusion in ducks (Anas platyrhynchos)

The intravenous infusion of somatostatin (800 ng/kg min) reduced the concentration of growth hormone (GH) in the plasma of 4 to 5, 6 to 7 and 8 to 9 week-old ducklings, but not in adult ducks. The inhibition of GH secretion was not due to accompanying changes in pancreatic function, since the infusion of a lower dose of somatostatin (200 ng/kg min) increased glucagon release and decreased plasma free fatty acids (FFA), as observed with the higher dose, but had no effect on GH concentrations. The withdrawal of somatostatin inhibition resulted in rebound GH secretion in immature birds, the magnitude of which was directly related to the pre-treatment level. Following somatostatin infusion (800 ng/kg min) no modification in GH concentration was observed in adult ducks. These results demonstrate that basal GH release in young birds is not autonomous and is suppressible by somatostatin. The data provide further evidence for age-related changes in the control of avian GH and insulin release and for the independence of the effects of somatostatin on the pituitary and pancreas glands.     

Equine trypsin: purification and development of a radio-immunoassay

Shock is accompanied by generalised splanchnic hypoperfusion, and splanchnic organs like the pancreas can be damaged, as shown in animal experimental models and in humans, by the presence of high plasma concentrations of trypsin and other pancreatic enzymes. In order to design a radioimmunoassay technique (RIA) for the measurement of equine trypsin-like immunoreactivity (TLI) in biological fluids, trypsin was purified (with purity > or = 96%) from the equine pancreas by extraction in an acid medium, ammonium sulfate precipitations, gel filtration chromatography and, after activation of trypsinogen into trypsin, affinity chromatography. Gel polyacrylamide electrophoresis showed a monomeric enzyme with a molecular weight of 27 kDa. The purified equine trypsin served for the immunisation of rabbits in order to obtain a specific antiserum, and the labelled antigen was prepared by iodination of equine trypsin with 125I. The RIA was based on the binding of the antigen to the antibody followed by the separation of the antigen-antibody complex by immunoprecipitation in the presence of sheep anti-rabbit gammaglobulins and the assay of the radioactivity in the precipitate. The RIA showed good sensitivity, specificity, precision, accuracy and reproducibility. The reference mean value of TLI in the plasma of healthy horses (n = 20) was 30.01+/-6.84 ng/mL (upper confidence limit 50.52 ng/mL; p < 0.01). Three horses with non strangulating intestinal obstruction without shock showed TLI values within normal limits whereas 5 of 7 horses with strangulation obstruction showed TLI levels above the upper confidence limit. Further studies using the RIA and the enzymatic assay should be performed in order to confirm the role of the pancreas in equine intestinal obstruction.     

Insulin dysregulation

Abnormalities of insulin metabolism include hyperinsulinaemia and insulin resistance, and these problems are collectively referred to as insulin dysregulation in this review. Insulin dysregulation is a key component of equine metabolic syndrome: a collection of endocrine and metabolic abnormalities associated with the development of laminitis in horses, ponies and donkeys. Insulin dysregulation can also accompany prematurity and systemic illness in foals. Causes of insulin resistance are discussed, including pathological conditions of obesity, systemic inflammation and pituitary pars intermedia dysfunction, as well as the physiological responses to stress and pregnancy. Most of the discussion of insulin dysregulation to date has focused on insulin resistance, but there is increasing interest in hyperinsulinaemia itself and insulin responses to feeding. An oral sugar test or in‐feed oral glucose tolerance test can be performed to assess insulin responses to dietary carbohydrates, and these tests are now recommended for use in clinical practice. Incretin hormones are likely to play an important role in postprandial hyperinsulinaemia and are the subject of current research. Insulin resistance exacerbates hyperinsulinaemia, and insulin sensitivity can be measured by performing a combined glucose‐insulin test or i.v. insulin tolerance test. In both of these tests, exogenous insulin is administered and the rate of glucose uptake into tissues measured. Diagnosis and management of hyperinsulinaemia is recommended to reduce the risk of laminitis. The term insulin dysregulation is introduced here to refer collectively to excessive insulin responses to sugars, fasting hyperinsulinaemia and insulin resistance, which are all components of equine metabolic syndrome.     

Pharmacokinetics,pharmacodynamics, and metabolism of acepromazine following intravenous,oral, and sublingual administration to exercised Thoroughbred horses

Acepromazine is a tranquilizer used commonly in equine medicine. This study describes serum and urine concentrations and the pharmacokinetics and pharmacodynamics of acepromazine following intravenous, oral, and sublingual (SL) administration. Fifteen exercised adult Thoroughbred horses received a single intravenous, oral, and SL dose of 0.09 mg/kg of acepromazine. Blood and urine samples were collected at time 0 and at various times for up to 72 hr and analyzed for acepromazine and its two major metabolites (2‐(1‐hydroxyethyl) promazine and 2‐(1‐hydroxyethyl) promazine sulfoxide) using liquid chromatography–tandem mass spectrometry. Acepromazine was also incubated in vitro with whole equine blood and serum concentrations of the parent drug and metabolites determined. Acepromazine was quantitated for 24 hr following intravenous administration and 72 hr following oral and SL administration. Results of in vitro incubations with whole blood suggest additional metabolism by RBCs. The mean ± SEM elimination half‐life was 5.16 ± 0.450, 8.58 ± 2.23, and 6.70 ± 2.62 hr following intravenous, oral, and SL administration, respectively. No adverse effects were noted and horses appeared sedate as noted by a decrease in chin‐to‐ground distance within 5 (i.v.) or 15 (p.o. and SL) minutes postadministration. The duration of sedation lasted 2 hr. Changes in heart rate were minimal.     

Inhibition of glucose-induced insulin secretion by somatostatin in goats

Somatostatin inhibited glucose-induced insulin secretion in intact goats. The duration of the inhibition was short (10 minutes) which suggests that somatostatin was rapidly metabolised. The inhibitory effect of somatostatin was followed by a recovery period during which high levels of insulin were attained. These higher concentrations of insulin in the 30 to 60 minutes after somatostatin infusion, were accompanied by lowered free fatty acid and beta-hydroxybutyrate concentrations. It is suggested that the effects of somatostatin on these metabolites is brought about by modulation of insulin secretion and not by a direct effect of somatostatin on target tissues.     

Glucose uptake in horses with polysaccharide storage myopathy

OBJECTIVE: To determine whether excessive glycogen accumulation in skeletal muscle of Quarter Horses with polysaccharide storage myopathy (PSSM) is a result of enhanced cellular uptake of glucose. ANIMALS: 6 horses with PSSM and 10 healthy (control) horses. PROCEDURE: Intravenous glucose tolerance tests (IVGTT), oral glucose tolerance tests (OGTT), and modified insulin tolerance tests (MITT) were performed. Plasma glucose and insulin concentrations were measured in blood samples collected before and for up to 8 hours after glucose or insulin administration. RESULTS: Peak glucose concentrations during IVGTT were similar for both groups of horses, but rate of glucose clearance was 1.5 times faster in horses with PSSM than in controls. Moreover, circulating concentrations of insulin before and after glucose injection were lower in the PSSM group. Blood glucose concentrations from minute 90 to minute 300 of the OGTT were lower in horses with PSSM than in controls. The MITT resulted in acute decreases in blood glucose concentrations in both groups of horses; however, horses with PSSM sustained low blood glucose concentrations for more than 3 hours after insulin injection, whereas blood glucose concentrations in controls returned to baseline values within 2 hours. CONCLUSIONS: Quarter Horses with PSSM have enhanced cellular uptake of glucose that may be, in part, caused by an increased sensitivity to insulin. CLINICAL RELEVANCE: Horses with PSSM have an increased rate of glucose clearance in response to insulin secretion. Thus, diets low in soluble carbohydrate may be the most effective way to decrease glycogen accumulation in skeletal muscle of these horses.