Effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses

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.     

Effects of short- and long-term recombinant equine growth hormone and short-term hydrocortisone administration on tissue sensitivity to insulin in horses

OBJECTIVE: To determine the effects of short-term IV administration of hydrocortisone or equine growth hormone (eGH) or long-term IM administration of eGH to horses on tissue sensitivity to exogenous insulin. ANIMALS: 5 Standardbreds and 4 Dutch Warmblood horses. PROCEDURE: The euglycemic-hyperinsulinemic clamp technique was used to examine sensitivity of peripheral tissues to exogenous insulin 24 hours after administration of a single dose of hydrocortisone (0.06 mg/kg), eGH (20 microg/kg), or saline (0.9% NaCl) solution and after long-term administration (11 to 15 days) of eGH to horses. The amounts of metabolized glucose (M) and plasma insulin concentration (I) were determined. RESULTS: Values for M and the M-to-I ratio were significantly higher 24 hours after administration of a single dose of hydrocortisone than after single-dose administration of eGH or saline solution. After long-term administration of eGH, basal I concentration was increased and the mean M-to-I ratio was 22% lower, compared with values for horses treated with saline solution. CONCLUSIONS AND CLINICAL RELEVANCE: Increases in M and the M-to-I ratio after a single dose of hydrocortisone imply that short-term hydrocortisone treatment increases glucose use by, and insulin sensitivity of, peripheral tissues. Assuming a single dose of hydrocortisone improves sensitivity of peripheral tissues to insulin, it may be an interesting candidate for use in reducing insulin resistance in peripheral tissues of horses with several disease states. In contrast, long-term administration of eGH decreased tissue sensitivity to exogenous insulin associated with hyperinsulinemia. Therefore, increased concentrations of growth hormone may contribute to insulin resistance in horses with various disease states.     

Effects of continuous or intermittent lipopolysaccharide administration for 48 hours on the systemic inflammatory response in horses

Objective-To determine whether the method of lipopolysaccharide (LPS) administration (intermittent vs continuous) affects the magnitude and duration of the systemic inflammatory response in horses and whether prolonged (48 hours) endotoxemia induces laminitis. Animals-12 healthy adult horses (10 mares and 2 geldings). Procedures-Horses were randomly assigned to receive LPS (total dose, 80 μg; n = 4) or saline (0.9% NaCl) solution (80 mL/h; 4) via constant rate infusion or 8 bolus IV injections of LPS (10 μg, q 6 h;4) during a 48-hour period. Physical examinations were performed every 4 hours, inflammatory cytokine gene expression was determined for blood samples obtained every 8 hours, and IV glucose tolerance tests were performed. Results-All LPS-treated horses had signs of depression and mild colic; those signs abated as the study progressed. Administration of LPS increased expression of interleukin-1β, interleukin-6, and interleukin-8, but results were not significantly different between LPS treatment groups. Cytokine expression was significantly higher on the first day versus the second day of LPS treatment. Interleukin-1β expression was positively correlated with rectal temperature and expression of other cytokines. Glucose and insulin dynamics for both LPS groups combined did not differ significantly from those of the saline solution group. Signs of laminitis were not detected in any of the horses. Conclusions and Clinical Relevance-Horses developed LPS tolerance within approximately 24 hours after administration was started, and the method of LPS administration did not affect the magnitude or duration of systemic inflammation. Laminitis was not induced in horses.     

脂肪组织的内分泌功能及其与肌肉组织间的分子信号联系

脂肪组织不仅是机体储存能量的主要场所,还是一个活跃的内分泌器官;骨骼肌同样也具有分泌活性物质的功能,能表达、合成和分泌多种生物信号分子。这些活性因子与许多重要的生理、病理过程有密切的关系。对脂肪组织的内分泌功能及其与肌肉组织间的分子信号联系进行了综述。     

脂肪组织的内分泌功能及其与肌肉组织间的分子信号联系

脂肪组织不仅是机体储存能量的主要场所,还是一个活跃的内分泌器官;骨骼肌同样也具有分泌活性物质的功能,能表达、合成和分泌多种生物信号分子。这些活性因子与许多重要的生理、病理过程有密切的关系。对脂肪组织的内分泌功能及其与肌肉组织间的分子信号联系进行了综述。     

Effects of low and high levels of maternal nutrition consumed for the entirety of gestation on the development of muscle,adipose tissue,bone, and the organs of Wagyu cattle fetuses

This study aimed to investigate the effects of high and low levels of energy intake during the entire gestation period on the skeletal muscle development, organ development, and adipose tissue accumulation in fetuses of Wagyu (Japanese Black) cows, a breed with highly marbled beef. Cows were allocated to a high-nutrition (n = 6) group (fed 120% of the nutritional requirement) or low-nutrition (n = 6) group (fed 60% of the nutritional requirement). The cows were artificially inseminated with semen from the same sire, and the fetuses were removed by cesarean section at 260 ± 8.3 days of fetal age and slaughtered. The whole-body, total muscle, adipose, and bone masses of the fetal half-carcasses were significantly higher in the high-nutrition group than the low-nutrition group (p = 0.0018, 0.009, 0.0004, and 0.0362, respectively). Fifteen of 20 individual muscles, five of six fat depots, nine of 17 organs, and seven of 12 bones that were investigated had significantly higher masses in the high-nutrition group than the low-nutrition group. The crude components and amino acid composition of the longissimus muscle significantly differed between the low- and high-nutrition groups. These data indicate that maternal nutrition during gestation has a marked effect on the muscle, bone, and adipose tissue development of Wagyu cattle fetuses.     

Effects of halothane and isoflurane on baroreflex sensitivity in horses

Baroreflex sensitivity (BS) was used to quantitatively assess the effects of halothane and isoflurane on the heart rate/arterial pressure relationship during steady-state (10 minutes) and dynamic pressure changes in adult horses. Arterial pressure was decreased in response to nitroglycerin or sodium nitroprusside and increased in response to phenylephrine HCl. Mean (+/- SEM) BS in awake horses was 28.9 +/- 2.6 and 13.2 +/- 2.0 ms/mm of Hg during steady-state decreases and increases in systolic arterial pressure (SAP), respectively. Halothane and isoflurane either significantly (P less than 0.05) decreased or eliminated BS during steady-state decreases in SAP, with no significant differences detected between anesthetic agents. During steady-state decreases in SAP, significant (P less than 0.05) correlation between R-R interval and arterial pressure was not observed for 6 of 10 and 4 of 11 halothane and isoflurane anesthesia periods, respectively. Halothane significantly (P less than 0.05) decreased BS during steady-state increases in SAP to 7.9 +/- 0.6 and 6.5 +/- 1.1 ms/mm of Hg during low and high minimal alveolar concentration (MAC) multiples, respectively. Isoflurane decreased BS during steady-state increases in SAP to 9.6 +/- 1.5 and 6.6 +/- 1.1 ms/mm of Hg during low and high MAC anesthesia, respectively, with high MAC of isoflurane decreasing BS significantly (P less than 0.05), compared with awake and low MAC values. Plasma catecholamine (epinephrine and norepinephrine) concentrations increased significantly (P less than 0.05), compared with baseline values during steady-state vasodilator infusions in halothane- and isoflurane-anesthetized horses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of oat processing on the glycaemic and insulin responses in horses

This study was conducted to evaluate the effects of different oat processing techniques on the plasma glucose and insulin response in horses. In a cross-over design, six horses (ages 4-15 years, mean body weight+/-SD: 450+/-37 kg) were fed in random order: untreated oats, finely ground, steam-flaked and popped oats. The total oat intake varied between 1.05-1.5 kg/day, and the amount of diet was adjusted to a starch content of 630 g starch per day and horse (1.2-1.5 g starch/kg BW/day). During the stabilization period of 10 days, horses additionally received 6 kg grass hay. Following this adaptation period, plasma glucose and insulin responses to the respective dietary treatments were tested. Horses were fed their test diet (exclusively oats), and blood samples were collected at defined times to determine glycaemic and insulin response. Oat feeding resulted in a significant increase in mean plasma glucose and insulin concentration. However, glucose and insulin peaks as well as their respective areas under the curves were not clearly influenced by oat processing. The glycaemic index varied between 94.7+/-11.2% (steam-flaked oats) and 102.6+/-14.5% (finely ground oats, n.s.), the insulin index ranged between 93.8+/-18.9% (popped oats) and 150.0+/-77.6% (finely ground oats, n.s.). The insulin reaction to oat feeding showed a high variability between the horses. The results of this study indicate that the glucose and insulin responses are not clearly altered by the different types of oat processing. However, the glucose and insulin responses tended to be lower in thermally treated oats when compared with untreated or finely ground oats.     

Fatty acid profile of plasma,muscle and adipose tissues in Chilota lambs grazing on two different low quality pasture types in Chiloé Archipelago (Chile)

There is no information about the effect of different pasture types on tissue fatty acid profiles of a native rustic lamb breed of the Chiloe Archipelago, the Chilota. Eight Chilota lambs were grazed on a ‘Calafatal’ pasture (CP), a typical secondary succession of Chiloé Archipelago (Chile) and eight Chilota lambs were located to graze on naturalized pasture (NP) of Chiloé. Botanical, chemical and lipid composition of the two types of pastures and of different lamb tissues (muscle, subcutaneous – and tail adipose tissues) and plasma were performed. Both pasture types induced high n‐3 polyunsaturated fatty acids (PUFA) and CLAcis‐9,trans‐11 proportions in Chilota meat. Thus, in muscle, Chilota lambs grazing CP showed higher sum PUFA, sum n‐6 PUFA proportion and n‐6/n‐3 PUFA ratio compared with Chilota lambs grazing NP. In tail fats of Chilota lambs grazing CP significantly higher proportions of 18:3n‐3, sum saturated fatty acids, sum PUFA, n‐3 and n‐6 PUFA were detected compared with Chilota lambs grazing NP. Feeding of different pasture types (CP vs. NP) caused significant differences in fatty acid composition of muscle and the two fat depots in Chilota lambs, but also point to tissue‐specific responses of de novo synthesized fatty acid deposition in the tissues.     

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.     

Effects of feeding pattern on ghrelin and insulin secretion in pigs

Ghrelin is a peptide hormone that has been implicated in the regulation of feed intake, but little is known about its secretion in pigs. Hence, the effect of feeding pattern on the regulation of ghrelin secretion was tested. In experiment 1, barrows were allotted randomly into 1 of 2 groups, (1) ad libitum fed (CONT) and (2) limited access to feed (once per day, MEAL). Blood samples were taken through jugular catheters every 15 min for 6 h after 7 d on the experimental feeding regimen. Plasma concentrations of ghrelin and insulin were determined by radioimmunoassay. Ghrelin concentrations in the MEAL pigs were elevated before feeding and declined after feeding (P < 0.01). No pattern in plasma ghrelin concentrations was observed in the CONT pigs, but ghrelin concentrations were lower than in the MEAL group. Insulin concentrations were greater in CONT pigs (P < 0.01) during most of the sampling and increased after feeding in the MEAL pigs (P < 0.01). In experiment 2, the treatments were the same as in experiment 1; however, the amount of feed was increased in the MEAL group so that their daily intake was similar to the CONT pigs. Ghrelin concentrations in the MEAL group were again elevated before the meal and declined afterward (P < 0.01). Insulin but not glucose concentrations were negatively correlated with ghrelin. Once-per-day feeding resulted in increased plasma concentrations of ghrelin, which decreased after feeding. Ghrelin may be involved in the regulation of feed intake in pigs.     

Effects of castration-induced visceral obesity and antioxidant treatment on lipid profile and insulin sensitivity in New Zealand white rabbits

Molecular mechanisms, responsible for the impaired insulin-sensitivity state due to the obesity are not fully understood in both humans and animals. The purpose of this study was to investigate the effects of castration-induced visceral obesity and the influence of two antioxidants on constituents of blood lipid profile and insulin sensitivity in New Zealand white rabbits. Twenty-six clinically healthy male New Zealand white rabbits were used in the experiment and were divided into 3 groups: first group (CI, n = 7) - castrated-obese and treated with antioxidants “Immunoprotect” for 2 months; second group (CO, n = 7) - castrated-obese; third group (NC, n = 12) - control group (non-castrated, non-obese). At the end of the follow-up period of 2 months after castration an intravenous glucose tolerance test (IVGTT) was performed after a 12-h fasting period as the blood samples for determination of glucose and insulin and their kinetic parameters were obtained at 5 and 0 min before and at 5, 10, 30, 60 and 120 min after the infusion of the glucose. The constituents of lipid profile, triglycerides (TG), total cholesterol (TC) and HDL-cholesterol (HDL-C) were also assessed in the overnight fasting blood samples. The body weight (BW), body mass index (BMI), amount of the visceral fat (VF) and VF/BW ratio were both measured and calculated before the IVGTT and at the end of the experimental period. All measured markers of obesity (BW, BMI, VF, VF/BW) were significantly higher in both groups of castrated rabbits than in the control group. Apart HDL-C, the plasma concentrations of all constituents of lipid profile (TG, TC, HDL-C) were the highest in CO group. There were generally no differences between CI and NC groups for the same traits. After glucose injection blood glucose concentrations and glucose and insulin kinetic parameters were considerably higher (except of glucose elimination rate) in CO rabbits than in NC ones. Castrated rabbits treated with “Immunoprotect” showed lower fasting plasma insulin and improved glucose kinetics dynamics than CO rabbits, but commensurable values of glucose and insulin kinetics parameters than NC group. The results of the current study clearly indicated that castration-induced visceral obesity affected negatively the lipid profile and insulin sensitivity and/or responsiveness. Treatment with antioxidant supplementation, consisted of d-limonene and vitamin E, improved blood lipid profile, fatty liver, glucose homeostasis and insulin sensitivity in obese rabbits. In addition, based on our results we may suggest that castrated male New Zealand white rabbits might be considered as an appropriate animal model to study various metabolic abnormalities related to visceral obesity, such as dyslipidemia and impaired insulin sensitivity.     

Effects of intravenous administration of peripheral blood‐derived mesenchymal stromal cells after infusion of lipopolysaccharide in horses

BackgroundA systemic and dysregulated immune response to infection contributes to morbidity and mortality associated with sepsis. Peripheral blood‐derived mesenchymal stromal cells (PB‐MSC) mitigate inflammation in animal models of sepsis. Allogeneic PB‐MSC administered IV to horses is well‐tolerated but therapeutic benefits are unknown.HypothesisAfter IV lipopolysaccharide (LPS) infusion, horses treated with PB‐MSC would have less severe clinical signs, clinicopathological abnormalities, inflammatory cytokine gene expression, and oxidative stress compared to controls administered a placebo.AnimalsSixteen horses were included in this study.MethodsA randomized placebo‐controlled experimental trial was performed. Sixteen healthy horses were assigned to 1 of 2 treatment groups (1 × 10⁹ PB‐MSC or saline placebo). Treatments were administered 30 minutes after completion of LPS infusion of approximately 30 ng/kg. Clinical signs, clinicopathological variables, inflammatory cytokine gene expression, and oxidative stress markers were assessed at various time points over a 24‐hour period.ResultsA predictable response to IV LPS infusion was observed in all horses. At the dose administered, there was no significant effect of PB‐MSC on clinical signs, clinicopathological variables, or inflammatory cytokine gene expression at any time point. Antioxidant potential was not different between treatment groups, but intracellular ROS increased over time in the placebo group. Other variables that changed over time were likely due to effects of IV LPS infusion.Conclusions and Clinical ImportanceAdministration of allogeneic PB‐MSC did not cause clinically detectable adverse effects in healthy horses. The dose of PB‐MSC used here is unlikely to exert a beneficial effect in endotoxemic horses.     

G蛋白偶联受体120在动物脂代谢及免疫调节中作用的研究进展

脂肪酸在动物脂质代谢和免疫调节中起着至关重要的作用,G蛋白偶联受体120(G-protein coupled receptor 120,GPR120)又被称为游离脂肪酸受体4(free fatty acid receptor 4,FFAR4)是G蛋白偶联受体家族成员。它可以被长链脂肪酸激活,参与调节机体糖脂代谢,是治疗人及畜禽脂质代谢紊乱及免疫调节等相关疾病的热点靶点。本文就近来GPR120在脂肪组织中的研究现状、对免疫调节的作用及其激动剂或配体作为药物运用的可能做一综述。