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Asplin KE Curlewis JD McGowan CM Pollitt CC Sillence MN 《Equine veterinary journal》2011,43(2):196-201
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. 相似文献
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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. 相似文献
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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. 相似文献
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Hayirli A 《Veterinary research communications》2006,30(7):749-774
As a result of a marked decline in dry matter intake (DMI) prior to parturition and a slow rate of increase in DMI relative
to milk production after parturition, dairy cattle experience a negative energy balance. Changes in nutritional and metabolic
status during the periparturient period predispose dairy cattle to develop hepatic lipidosis and ketosis. The metabolic profile
during early lactation includes low concentrations of serum insulin, plasma glucose, and liver glycogen and high concentrations
of serum glucagon, adrenaline, growth hormone, plasma β-hydroxybutyrate and non-esterified fatty acids, and liver triglyceride.
Moreover, during late gestation and early lactation, flow of nutrients to fetus and mammary tissues are accorded a high degree
of metabolic priority. This priority coincides with lowered responsiveness and sensitivity of extrahepatic tissues to insulin,
which presumably plays a key role in development of hepatic lipidosis and ketosis. Hepatic lipidosis and ketosis compromise
production, immune function, and fertility. Cows with hepatic lipidosis and ketosis have low tissue responsiveness to insulin
owing to ketoacidosis. Insulin has numerous roles in metabolism of carbohydrates, lipids and proteins. Insulin is an anabolic
hormone and acts to preserve nutrients as well as being a potent feed intake regulator. In addition to the major replacement
therapy to alleviate severity of negative energy balance, administration of insulin with concomitant delivery of dextrose
increases efficiency of treatment for hepatic lipidosis and ketosis. However, data on use of insulin to prevent these lipid-related
metabolic disorders are limited and it should be investigated. 相似文献
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S.R. Byers O.M. Beemer A.S. Lear R.J. Callan 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2014,28(5):1613-1620
Background
Persistent hyperglycemia is common in alpacas and typically requires insulin administration for resolution; however, little is known about alpacas’ response to different insulin formulations.Objectives
To evaluate the effects of 3 insulin formulations on blood glucose concentrations and the use of a continuous glucose monitoring (CGM) system in alpacas.Animals
Six healthy alpacas.Methods
The CGM was installed in the left paralumbar fossa at the start of this crossover study and recorded data every 5 minutes. Regular insulin, NPH insulin, insulin glargine, and dextrose were administered to each alpaca over a 2‐week period. Blood samples were collected for glucose testing at 0, 1, 2, 4, 6, 8, and 12 hours, and then every 6 hours after each administration of insulin or dextrose. Data were compared by using method comparison techniques, error grid plots, and ANOVA.Results
Blood glucose concentrations decreased most rapidly after regular insulin administration when administered IV or SC as compared to the other formulations. The NPH insulin produced the longest suppression of blood glucose. The mean CGM interstitial compartment glucose concentrations were typically lower than the intravascular compartment glucose concentrations. The alpacas had no adverse reactions to the different insulin formulations.Conclusions and Clinical Importance
The NPH insulin might be more appropriate for long‐term use in hyperglycemic alpacas because of its extended duration of action. A CGM is useful in monitoring glucose trends and reducing blood collection events, but it should not be the sole method for determining treatment protocols. 相似文献9.
F. TÓTH N. FRANK S. B. ELLIOTT K. PERDUE R. J. GEOR R. C. BOSTON 《Equine veterinary journal》2009,41(9):844-851
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. 相似文献
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Takumi KOMIYA Akihiro MORI Naohito NISHII Hitomi ODA Eri ONOZAWA Seri SEKI Toshinori SAKO 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2021,83(4):661
A 5-year-old castrated male domestic shorthair cat was diagnosed with diabetic ketoacidosis and severe insulin resistance. Although the conventional treatment for diabetic ketoacidosis was provided, the cat required frequent hospitalization because of severe dehydration and repeated diabetic ketoacidosis. We detected anti-insulin antibodies for human in this cat. Serum insulin-binding IgG levels were markedly elevated compared with those in healthy cats and other diabetic cats. We initiated prednisolone to suppress the effects of anti-insulin antibodies. After initiation of prednisolone, the cat was gradually recovered with increasing activity and appetite. Furthermore, satisfactory glycemic control was achieved with combined subcutaneous injection of insulin detemir and insulin degludec. 相似文献
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Effects of the sodium‐glucose cotransporter 2 (SGLT2) inhibitor velagliflozin,a new drug with therapeutic potential to treat diabetes in cats 
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下载免费PDF全文 M. Hoenig M. Clark D. J. Schaeffer D. Reiche 《Journal of veterinary pharmacology and therapeutics》2018,41(2):266-273
Sodium‐glucose cotransporter 2 (SGLT2) inhibitors are used in the treatment of human diabetics. They increase glucose excretion and correct hyperglycemia. We examined the investigational SGLT2 inhibitor velagliflozin in two groups of six neutered adult obese cats (equal gender distribution). Placebo (Pl) or drug (D; 1 mg/kg) was administered for 35 days. Routine blood examinations, fructosamine, beta‐hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), glucagon, adiponectin, and leptin were measured before and after treatment, also water intake, and urinary electrolytes, glucose, and volume. Indirect calorimetry, an intravenous glucose tolerance test (IVGTT; 0.8 g/kg) and insulin tolerance test (IVITT) were conducted. All cats tolerated treatment well. Significant changes with D included a decrease in the respiratory exchange ratio, an increase in cholesterol, a small increase in albumin, and a rise in BHB and NEFA. Glucose clearance was unaltered, although less insulin was secreted during the IVGTT (p = .056) suggesting improved insulin sensitivity. IVITT was unchanged. Treatment did not affect glucagon, leptin, or adiponectin. Water intake, urine output, urinary glucose excretion, and the glucose/creatinine ratio but not urinary electrolytes were significantly higher post‐D. We conclude that velagliflozin is a promising drug, which increases urinary glucose excretion in cats and could thereby be beneficial for the treatment of hyperglycemia. 相似文献
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The acute metabolic effects of clenbuterol were studied in calves. Clenbuterol was given intravenously at a dose of 1 µg/kg body weight. Glucagon was used to increase insulin secretion. Pretreatment with clenbuterol did not change the glucagon-induced hyperglycaemia, but the serum levels of insulin were significantly higher. Clenbuterol showed a significant lipolytic effect. The post prandial increases in glucose and insulin were significantly higher in clenbuterol treated calves. The findings are in accordance with results from earlier studies where clenbuterol was given orally in much higher doses. 相似文献
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F. TÓTH N. FRANK T. MARTIN‐JIMÉNEZ S. B. ELLIOTT R. J. GEOR R. C. BOSTON 《Equine veterinary journal》2010,42(2):149-155
Reasons for performing study: Hyperinsulinaemia is detected in horses with insulin resistance (IR) and has previously been attributed to increased pancreatic insulin secretion. Connecting peptide (C‐peptide) can be measured to assess pancreatic function because it is secreted in equimolar amounts with insulin and does not undergo hepatic clearance. Hypothesis: A human double antibody radioimmunoassay (RIA) detects C‐peptide in equine serum and concentrations would reflect responses to different stimuli and conditions. Methods: A validation procedure was performed to assess the RIA. Six mature mares were selected and somatostatin administered i.v. as a primed continuous rate infusion, followed by 50 nmol human C‐peptide i.v. Insulin and C‐peptide concentrations were measured in horses (n = 6) undergoing an insulin‐modified frequently sampled i.v. glucose tolerance test, and in horses with insulin resistance (n = 10) or normal insulin sensitivity (n = 20). Results: A human RIA was validated for use with equine sera. Endogenous C‐peptide secretion was suppressed by somatostatin and median (range) clearance rate was 0.83 (0.15–1.61) ml/min/kg bwt. Mean ± s.d. C‐peptide‐to‐insulin ratio significantly (P = 0.004) decreased during the glucose tolerance test from 3.60 ± 1.95 prior to infusion to 1.03 ± 0.18 during the first 20 min following dextrose administration. Median C‐peptide and insulin concentrations were 1.5‐ and 9.5‐fold higher, respectively in horses with IR, compared with healthy horses. Conclusions: Endogenous C‐peptide secretion decreases in response to somatostatin and increases after dextrose infusion. Results suggest that relative insulin clearance decreases as pancreatic secretion increases in response to dextrose infusion. Hyperinsulinaemia in insulin resistant horses may be associated with both increased insulin secretion and decreased insulin clearance. Potential relevance: Both C‐peptide and insulin concentrations should be measured to assess pancreatic secretion and insulin clearance in horses. 相似文献
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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. 相似文献
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Summary Examination of nearly 2000 sera indicated that approximately 90 per cent of cattle had acquired Dictyocaulus viviparus infections during the previous grazing season. No differences were found between provinces. Large differences were seen between herds. Antibody titres of milk cows on zerograzing farms were significantly lower than on comparable farms where animals were pastured. The need for further epidemiological work is stressed. In such work serology can be helpful. 相似文献
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Davison LJ Walding B Herrtage ME Catchpole B 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2008,22(6):1317-1325
Background: Anti‐insulin antibodies (AIA) occur in diabetic dogs after insulin therapy, although their clinical significance is unclear. Hypothesis: Treatment of diabetic dogs with heterologous insulin is more likely to stimulate production of AIA than is treatment with homologous insulin. Animals: Diabetic dogs sampled before insulin therapy (n = 40), diabetic dogs sampled following treatment with porcine (homologous) insulin (n = 100), bovine (heterologous) lente insulin (n = 100), or bovine protamine zinc (PZI) insulin (n = 20), and nondiabetic control dogs (n = 120). Methods: Prospective observational study. Sera were analyzed by ELISA for antibodies against porcine insulin, bovine insulin, insulin A, B, or C peptides, and control antigens; canine distemper virus (CDV) and canine thyroglobulin (TG). Canine isotype‐specific antibodies were used to determine total and anti‐insulin IgG1 : IgG2 ratios. Results: There was no difference in CDV or TG reactivity among the groups. AIA were detected in 5 of 40 newly diagnosed (untreated) diabetic dogs. There was no significant difference in AIA (ELISA optical density reactivity) comparing control and porcine insulin‐treated diabetic dogs (P > .05). Anti‐insulin reactivity was most prevalent in bovine PZI insulin‐treated dogs (90%; P < .01), and bovine lente insulin‐treated dogs (56%; P < .01). AIA induced by treatment were enriched for the IgG1 isotype. Conclusions and Clinical Importance: This study indicates that bovine insulin is more immunogenic than porcine insulin when used for treatment of diabetic dogs. 相似文献
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本试验旨在研究胰岛素受体-1(IR-1)在尼罗罗非鱼不同组织中的表达及其对注射葡萄糖的响应。利用PCR扩增的方法从尼罗罗非鱼肌肉中克隆IR-1的c DNA片段,并通过半定量PCR检测,比较IR-1在肌肉、肝脏和心脏中的表达差异。选取体重约为100 g的尼罗罗非鱼160尾,随机分2组,每组4个重复,每个重复20尾。试验组腹腔注射葡萄糖(每100 g体重30 mg),对照组以相同剂量腹腔注射0.7%的无菌生理盐水。在注射前(0 h)和注射后的1、3、6和12 h分别进行采样,测定血浆葡萄糖和胰岛素含量,并通过实时荧光定量PCR检测IR-1在肌肉、心脏和肝脏中的mRNA相对表达量。结果显示:1)克隆出的IR-1 c DNA片段,其Gen Bank登陆号为JN967750,大小为1 979 bp,编码548个氨基酸。序列分析发现,尼罗罗非鱼的IR-1与其他物种比较具有很高的保守性,并具有丰富的酪氨酸激酶特征性序列。2)IR-1在尼罗罗非鱼肌肉、心脏和肝脏中均有较高的表达量,其中在肝脏和肌肉中的表达量基本一致,而在心脏中的表达量相对较低。3)试验组血浆葡萄糖含量在注射葡萄糖1 h后达到最高,并显著高于对照组(P0.05),而后开始下降,3 h后恢复到正常水平;试验组血浆胰岛素含量在葡萄糖注射3 h后达到最高,并显著高于对照组(P0.05),而后开始下降,12 h后恢复到正常水平。试验组肌肉和肝脏中IR-1 mRNA的相对表达量在注射葡萄糖后6 h时达到最高,显著高于对照组(P0.05),在12 h时恢复到正常水平;试验组心脏中IR-1 mRNA的相对表达量在注射葡萄糖后的12 h内没有发生显著变化(P0.05)。结果表明,注射葡萄糖后即刻升高了尼罗罗非鱼的血浆葡萄糖含量,相对于血浆葡萄糖含量的升高,血浆胰岛素含量的升高相对延迟,而肌肉和肝脏中IR-1 mRNA相对表达量的提高又延迟于血浆胰岛素含量的升高,从而加重了尼罗罗非鱼对葡萄糖的代谢负担。 相似文献
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The impact of the chromium supplementation on insulin signalling pathway in different tissues and milk yield in dairy cows 下载免费PDF全文
下载免费PDF全文 M. Pantelić L. J. Jovanović R. Prodanović I. Vujanac M. Đurić T. Ćulafić S. Vranješ‐Đurić G. Korićanac D. Kirovski 《Journal of animal physiology and animal nutrition》2018,102(1):41-55
Thirty days before expected time of parturition, 20 Holstein cows were divided into ?Cr and +Cr groups. From day 25 before parturition (BP ) up to day 30 after parturition (AP ), +Cr cows received 10 mg of Cr (chromium‐enriched yeast) daily. Muscle and adipose tissue samples were taken at days ?30, ?10, +7 and +10 related to parturition, when body condition score (BCS ) was also determined. Hepatic tissue samples were taken at days ?10 and +7. Tissue samples were used for determination of the insulin signalling pathway protein expressions. Intravenous glucose tolerance test (IVGTT ) was performed at days ?28, ?7, +10 and +30. Milk yield was recorded during first 14 weeks AP . Milk composition was obtained at days 7 and 28 AP . At day 10 BP , protein content of β ‐subunit of insulin receptor (IR β ) was significantly higher (p ? 0.05) in muscle, and phosphorylation of insulin receptor substrate 1 at serine 307 (pIRS ‐1 Ser307) was significantly lower (p ? 0.05) in hepatic tissue of +Cr group. After parturition, pIRS ‐1 Ser307 was significantly lower in muscle tissue at days 7 and 28 (p ? 0.05 and p ? 0.001, respectively), while phosphorylation of Akt at serine 473 (pA kt Ser473) was significantly higher (p ? 0.01) in hepatic tissue at day 7 AP in +Cr group. Chromium had opposite effect on insulin kinetics during IVGTT s obtained BP and AP . Insulin secretion was significantly reduced at day 7 BP and significantly enhanced at day 10 AP , when NEFA concentration was also significantly increased. Milk yield and ECM value were depressed in +Cr group. DMI and BCS were significantly enhanced in +Cr group at day 7 BP . In conclusion, chromium modulates insulin signalling pathway in dairy cows, but targeted signalling molecules are different in antepartal then post‐partal period, probably due to duration of exposure to chromium and different energy status between those periods. 相似文献