Time-action profiles of insulin detemir in normal and diabetic dogs

Insulin detemir is the first member of a new class of long-acting soluble insulin analogues capable of maintaining the basal level of insulin in humans. In this preliminary study, we investigated the time-action profiles of insulin detemir in normal and diabetic dogs since the use of insulin detemir in canines has yet to be determined. Eight animals were used in our study (three normal and five insulin dependent diabetic dogs). Time-action profiles of insulin detemir were monitored in normal dogs using an artificial pancreas apparatus under euglycemic condition. Blood sampling was performed at 2 h intervals post feeding, with insulin administration, in insulin dependent diabetic dogs. Time-action profiles of insulin detemir, in normal dogs, demonstrated that insulin detemir is a long-lasting preparation similar to what has been observed in humans. A pronounced peak was detected at 8–10 h while the glucose-lowering effect lasted for over 24 h after insulin injection, thus illustrating its longer prolonged peak activity time. Furthermore, intensive glycemic control was achieved with insulin detemir in insulin dependent diabetic dogs, using a lower dosage than NPH insulin and insulin glargine therapeutic doses. Our results indicate that insulin detemir has a greater effect than either NPH insulin or insulin glargine in canines, requiring a lower dose than either insulin preparation. However, using insulin detemir also carries a higher risk of inducing hypoglycemia as compared to either NPH insulin or insulin glargine.     

Comparison of time-action profiles of insulin Glargine and NPH insulin in normal and diabetic dogs

Intermediate insulin injections are commonly used for glycemic control in insulin dependent diabetic dogs acting as a replacement for natural insulin. Neutral Protamin Hagedorn (NPH) insulin and insulin glargine are two types of injectable insulin preparations commonly used in humans. In our study, we investigated the time-action profiles of both aforementioned insulin preparations in normal dogs in order to determine whether co-administration of NPH and glargine would be of benefit to insulin dependent diabetic dogs as it is for humans suffering from insulin dependent diabetes. Time-action profiles of NPH insulin and insulin glargine in normal dogs demonstrated a clear difference between both insulin preparations confirming that NPH insulin is an intermediate-acting preparation whereas insulin glargine is a long-lasting preparation. In addition, co-administration of NPH insulin and insulin glargine resulted in tight glycemic control as compared to NPH insulin alone in insulin dependent diabetic dogs. However, co-administration result in hypoglycemia at the dosages tested.     

Novel findings regarding Glut-4 expression in adipose tissue and muscle in horses--a preliminary report

One of the hallmarks of insulin resistance is a reduction in glucose transporter-4 (Glut-4) expression in adipose tissue but not in skeletal muscle. However, while Glut-4 has been demonstrated in skeletal and cardiac muscles in horses it has not been demonstrated in adipose tissue. The initial objectives of the present study were: (1) to test the hypothesis that Glut-4 expression would vary between selected key skeletal muscles; (2) to test the hypothesis that it would also vary between representative adipose tissue depots, and (3) to see whether expression would be greater in adipose tissue compared to muscle. Glut-4 expression was determined by Western blot using samples obtained from post mortem biopsies obtained from four muscles (gluteus medius, semitendinosus, heart, and diaphragm), and four adipose tissues (subcutaneous, retroperitoneal, mesenteric, and omental) in three horses. There were no differences (P>0.05) in Glut-4 protein expression between the muscles sampled. Likewise there were no differences (P>0.05) in Glut-4 protein expression between fat depots. There was a significant difference (P=0.03) when pooled means for Glut-4 expression in muscle (58.8+/-2.5 densitometry units) were compared with adipose tissue (115.8+/-15.7). This difference in Glut-4 expression in these two tissues with distinctly different metabolic reasons for taking up glucose may warrant further investigation to see if there are more pronounced differences in Glut-4 expression in muscle and adipose tissue in various populations of horses.     

Oral glucose leads to a differential response in glucose,insulin, and GLP-1 in lean versus obese cats

The response to oral glucose was examined in 10 obese and 9 lean age-matched, neutered cats. In all cats, oral administration of 2 g/kg glucose was followed by a prompt increase in glucose, insulin, and glucagon-like peptide (GLP)-1. There were significant differences between lean and obese cats in the areas under the curve for glucose, insulin, and GLP-1. However, the responses were variable, and a clear distinction between individual lean and obese cats was not possible. Therefore, this test cannot be recommended as a routine test to examine insulin resistance in individual cats as it is used in people. A further disadvantage for routine use is also the fact that this test requires gastric tubing for the correct administration of the glucose and associated tranquilization to minimize stress and that it was associated with development of diarrhea in 25% of the cats. GLP-1 concentrations were much lower in obese than lean cats. The low GLP-1 concentrations in obese cats might indicate a contribution of GLP-1 to the lower insulin sensitivity of obese cats, but this hypothesis needs to be further investigated.     

Some aspects of erythrocyte metabolism in insulin-treated diabetic dogs

Insulin-dependent diabetes mellitus (IDDM) is a common metabolic disease often complicated by a number of pathological conditions among which are haematological changes and alterations in blood cell function. Human and feline diabetes mellitus patients have been reported to be associated with oxidative stress that can lead to membrane alterations and to reduced erythrocyte life-span. Erythrocyte function in dogs affected by IDDM has been investigated during insulin therapy, paying attention to antioxidant status, membrane resistance, enzyme activities and 2,3-diphosphoglycerate (2,3DPG) concentration. Thirteen diabetic and 36 healthy dogs were bled and haematology and blood chemistry assays were performed to evaluate the degree of compensation. Osmotic fragility, the activities of the enzymes glucose-6-phosphate dehydrogenase (G6PD) and pyruvate-kinase (PK) and the concentrations of reduced glutathione (GSH) and 2,3DPG were evaluated in the erythrocytes. Diabetic dogs did not differ from controls in terms of haematological parameters, except for higher numbers of platelets. Higher values of fructosamine, glucose, protein, plasma potassium and calculated osmolality were detected in the plasma from diabetic dogs. No differences were detected in osmotic fragility, GSH concentration and PK activity between the two groups but 2,3DPG concentration and G6PD activity were statistically significantly higher in the diabetic group. The results indicate minimal alterations in erythrocyte functions occur in insulin-treated diabetic dogs. This contrasts with what has been reported for IDDM humans and cats.     

The Effects of Nonstructural Carbohydrate Content and Feeding Rate on Glucose and Insulin Response to Meal Feeding in Equine

The following research encompassed two experiments and involved feeding horses two isocaloric diets (diet A and diet B), with an approximate 50% difference in nonstructural carbohydrate (NSC) content. There were three main objectives: first, to test the hypothesis that feeding an approximately 50% lower NSC concentrate feed would cause a lower glucose and insulin response; second, to test the hypothesis that feeding meals equal in NSC content would create similar responses in glucose and insulin dynamics; and finally, to test the hypothesis that the time spent eating is correlated with glucose/insulin response. In experiment 1, in which diet A and diet B were fed at the same rate, the main finding was that feeding a meal lower in NSC resulted in a lower glucose and insulin response to the feed. In experiment 2, in which the effects of feeding diets A and B at a rate to provide 0.3 g/kg body weight (BW) NSC per meal were explored, the main finding was that, although glucose responses were similar, the meal containing more NSC/kg and fed at the lower rate resulted in a substantially lower insulin response. Consumption time also was found to be significantly different between treatments.In conclusion, a low NSC formulation and small meal size appear to be sensible recommendations for horses that may benefit from a low glucose and insulin response to feeding. In addition to NSC content, meal size, and nutrient:calorie ratio, nutrient requirements of the individual horse and the entire nutritional balance of the diet also should be addressed.     

The Effects of Feed Form on Consumption Time and Glucose and Insulin Response to a Concentrate Meal in Equine

This study tested the hypothesis that feeding an identically formulated, low sugar and starch concentrate in three forms (5-mm extruded [E], 4-mm pellet [P], and 19-mm oval [O]) would affect consumption rate and glucose or insulin responses, or both. Horses received 1.8 kg treatment feed in a randomized, crossover design, with samples taken every 30 minutes for 6 hours for blood glucose and insulin response. Pearson's correlation compared consumption time, insulin and glucose peak, and time to peak insulin and glucose. The pellet (P) elicited a lower (P = .01) glucose concentration at 2.5 hours than O. The pellet also elicited a lower (P = .03) insulin concentration at 5.5 hours than E and O. There were no differences (P > .05) in area under the curve (AUC) insulin, peak insulin, and time to peak insulin for the three treatments. Average insulin concentration was lower (P = .01) for P versus O. There were no differences (P > .05) in average insulin between P and E, nor between O and E. There were no differences (P > .05) in AUC and peak glucose concentration. Time to peak glucose was longer (P = .04) for P versus E. Average glucose concentration was lower (P = .02) for P versus O. Consumption time was longer (P = .03) for O versus P. There was a positive correlation between consumption time and time to peak insulin (r = 0.46, P = .029). Further research on feeding practices, feed forms, and consumption times that affect glycemic response is necessary.     

Characterization of Glucose Response Curves after Insulin Injection in Sensitive versus Insensitive Mares

The glucose responses to intravenous injections of a range of doses of recombinant human insulin were determined for six mares known to be insulin sensitive and six mares known to be insulin insensitive, with the goal of better characterizing the regression lines resulting from the two categories of mares. Insulin doses between 8 and 198 mU of insulin per kg of body weight (mU/kg BW) were administered intravenously between September 13 and 26, 2010, starting with 50 mU/kg BW on the first day. Higher and lower doses were administered on alternate days to obtain percentages of decreases in blood glucose concentrations between 10% and 70%. Linear regression analysis revealed that insulin-insensitive mares have glucose response curves with higher y intercepts (P = .066), less steep slopes (P = .0003), and less goodness of fit (P = .053) in addition to the expected greater dose required to produce a 50% reduction in blood glucose concentrations (ED50; P = .006), despite the similarities between their body weights and those of insulin-sensitive mares. Linear and nonlinear regression of responses to the 32, 50, and 79 mU/kg BW insulin doses with the overall estimates of ED50 and the natural log of ED50 indicated that the 50 mU/kg BW dose had the greatest coefficient of determination (>0.95). Generally, it appears that estimates of insulin sensitivity based on a single injection of insulin or on multiple injections of insulin are least variable for insulin-sensitive mares.     

Enhanced or Reduced Fetal Growth Induced by Embryo Transfer Into Smaller or Larger Breeds Alters Postnatal Growth and Metabolism in Weaned Horses

Embryo transfer between breeds of different sizes impacts fetal growth in horses. We have shown that it elicits various postnatal adaptations in terms of growth and glucose metabolism until weaning. Postweaning effects remain to be described. Pony (P), saddlebred (S), and draft (D) horses were used. Control Pony-in-Pony (P-P; n = 21) and Saddlebred-in-Saddlebred (S-S; n = 28) pregnancies were obtained by artificial insemination. Enhanced and restricted pregnancies were obtained by transferring P or S embryos into D mares (Pony-in-Draft [P-D], n = 6 and Saddlebred-in-Draft [S-D], n = 8) and S embryos into P mares (Saddlebred-in-Pony [S-P], n = 6), respectively. Control and experimental foals were raised by their dams and recipient mothers, respectively and weaned on day 180. Weight gain, growth hormones, and glucose metabolism were investigated in foals between days 180 and 540. Pony-in-Draft (P-D) remained heavier than P-P on days 180, 360, and 540, with lower glucose and higher non-esterified fatty-acids on days 180, 360, and 540 and higher T₃ on day 180. Insulin sensitivity was similar between pony groups on days 200 and 540. S-P were lighter than S-D on day 180 but caught up by day 540. S-P had higher glucose than S-D on days 180, 360, and 540, as well as lower non-esterified fatty-acids and higher T₃ on day 180. Insulin sensitivity was higher in S-P than in S-D on day 200. No difference was observed between saddlebred groups thereafter. In conclusion, in horses, fetal growth is determinant for postnatal metabolism, especially for energy availability.     

Insulin Sensitivity in Thoroughbred Geldings: Effect of Weight Gain,Diet, and Exercise on Insulin Sensitivity in Thoroughbred Geldings

The effects of dietary energy source, controlled weight gain, and exercise restriction on insulin sensitivity (SI) were studied in mature Thoroughbred geldings with body condition scores (BCS) of 4.3 ± 0.1. Two dietary energy sources were used, one high in starch and sugar (HS; n = 9) and one high in fat and fiber (HF; n = 7), and horses were fed 20 Mcal digestible energy (DE)/day above maintenance requirements to encourage weight gain. Using the minimal model of glucose and insulin dynamics, no differences in SI between groups were noted before initiation of treatment concentrate feeding. After dietary acclimation, SI was decreased in HS (P < 0.01) as compared with HF. After 32 weeks of controlled weight gain (90.8 kg; final BCS, 7.0 ± 0.1), SI remained lower in HS (P = 0.07) but did not change from the preweight gain value. SI in HF did not change between the start and end of weight gain. After completion of weight gain, exercise was restricted for 2 weeks, resulting in a reduction in SI in HF (P = 0.03) but no change in HS. It was concluded that dietary energy source may be more influential than weight gain on SI in the mature Thoroughbred gelding between BCS 4 and 7. The higher SI found in horses consuming the HF diet appeared to be partially dependent on some level of physical activity.     

Effect of octreotide on plasma concentrations of glucose, insulin, glucagon, growth hormone, and cortisol in healthy dogs and dogs with insulinoma

The inhibitory effect of the somatostatin analogue octreotide on the secretion of insulin could be used in the treatment of insulinoma. However, current information on the effectiveness of octreotide in dogs is conflicting. Therefore, the endocrine effects of a single subcutaneous dose of 50 microg octreotide were studied in healthy dogs in the fasting state (n=7) and in dogs with insulinoma (n=12). Octreotide did not cause any adverse effects. In healthy dogs in the fasting state, both plasma insulin and glucagon concentrations declined significantly. Basal (non-pulse related) GH and ACTH concentrations were not affected. A slight but significant decrease in the plasma glucose concentrations occurred. Dogs with insulinoma had significantly higher baseline insulin concentrations and lower baseline glucose concentrations than healthy dogs in the fasting state. Plasma glucagon, GH, ACTH, and cortisol concentrations did not differ from those in healthy dogs. Baseline plasma insulin concentrations decreased significantly in dogs with insulinoma after octreotide administration, whereas plasma concentrations of glucagon, GH, ACTH, and cortisol did not change. In contrast to the effects in the healthy dogs, in the dogs with insulinoma plasma glucose concentrations increased. Thus, the consistent suppression of plasma insulin concentrations in dogs with insulinoma, in the absence of an suppressive effect on counter-regulatory hormones, suggests that further studies on the effectiveness of slow-release preparations in the long-term medical treatment of dogs with insulinoma are warranted.     

克伦特罗对绵羊肝脏挥发性脂肪酸和糖代谢的影响

在 4头门静脉、肝静脉、颈静脉、肠系膜静脉和股动脉上安装血管导管的绵羊中研究了克伦特罗 (CL ,0 8mg/kgBW ,肠系膜静脉给药每天 2次 ,连续 5d)对其肝脏物质代谢的影响。结果表明 :CL可增加绵羊肝脏中的VFA流量 ,其中门静脉处乙酸、丙酸和丁酸的流量分别较对照期增加 19 4 9% (P <0 .0 1)、2 0 2 % (P >0 .0 5 )和4 5 5 % (P >0 .0 5 ) ,而肝静脉处VFA流量两期水平接近。CL也提高肝脏中葡萄糖的异生作用 ,在肝静脉处血中葡萄糖流量上升了 2 5 96 % (P <0 .0 1)。门静脉处血中葡萄糖循环水平也相应提高。此外在CL作用下肝静脉处胰岛素水平也较对照期有所下降。提示CL可增加进入绵羊肝脏中VFA的流量并促进肝脏对VFA的吸收和利用。通过降低胰岛素水平或对肝脏的直接作用CL还可增加绵羊血中葡萄糖的水平     

Clinical significance of plasma mannose concentrations in healthy and diabetic dogs

Circulating levels of monosaccharides can act as a reflection of systemic glucose/ energy metabolism. Characteristic changes observed in these levels can be seen in patients with diabetes and other metabolic disorders. There have been a few reports describing the significance of mannose metabolism as an energy source under physiological and pathological conditions. However, the relationship between circulating levels of mannose and the pathophysiology of diabetes mellitus are unknown in dogs. This study examined circulating levels of mannose between healthy control and diabetic dogs and evaluated the clinical significance of mannose levels in dogs. Diabetic dogs demonstrated a higher circulating level of mannose in comparison to normal healthy control dogs. Plasma mannose was positively correlated with plasma glucose and fructosamine, respectively. Interestingly, plasma mannose levels were affected by plasma insulin levels. In the context of feeding and glucose tolerance tests, plasma mannose levels responded to changes in circulating insulin levels. Circulating plasma mannose levels decreased after feeding in both control and diabetic animals in spite of observed insulin level differences. However, when glucose tolerance tests were given, a positive correlation between mannose levels and insulin levels was observed. Therefore, plasma mannose levels obtained via glucose tolerance testing may be used as a new diagnostic method for evaluating insulin resistance or deficiency in diabetic dogs.     

Treatment of Neonatal Calf Diarrhea with an Oral Electrolyte Solution Supplemented with Psyllium Mucilloid

Dairy calves under 14 days of age with naturally occurring, uncomplicated diarrhea were treated for 3 days with a hypertonic oral electrolyte solution with (n = 15) or without (n = 12) psyllium. Clinical response and clinical pathology data were compared between the 2 groups. Glucose absorption was evaluated on days 1 and 3 by measurement of plasma glucose and lactate and serum insulin concentrations for 4 hours after formula administration. On day 1, glucose, lactate, and insulin concentrations were lower in psyllium-fed calves than in control calves, with significant differences noted in glucose and lactate concentrations at several time points ( P < 0.05). Plasma lactate concentrations were higher at several times in both treatment groups on day 3 than on day 1 ( P < 0.05). Fecal consistency was markedly different in psyllium-fed calves as compared with control calves within 24 hours of psyllium supplementation. Fecal percent dry matter content was lower in psyllium-fed calves than in control calves at least once a day during supplementation and on day 3 compared with day 0 in the psyllium-fed calves ( P < 0.05). There were no significant differences in clinical performance scores, hydration status, arterial blood gas, serum anion gap, electrolyte, or total CO, concentrations. Addition of psyllium to an oral electrolyte solution resulted in immediate alterations in glucose absorption without impairing rehydration in diarrheic calves, but differences were transient and did not affect clinical outcome.     

Serum zinc, chromium, and iron concentrations in dogs with lymphoma and osteosarcoma

We compared serum concentrations of zinc, chromium, and iron in dogs with cancer to those of normal dogs. Dogs with lymphoma (n = 50) and osteosarcoma (n = 52) were evaluated. Dogs with lymphoma had significantly lower (P = .0028) mean serum zinc concentrations (mean +/- SD; 1.0 +/- 0.3 mg/L) when compared to normal dogs (1.2 +/- 0.4 mg/L). Dogs with osteosarcoma also had lower mean serum zinc concentrations (1.1 +/- 0.4 mg/L), but this difference was not significant (P = .075). Serum chromium concentrations were significantly lower in dogs with lymphoma (2.6 +/- 2.6 microg/L, P = .0007) and osteosarcoma (2.4 +/- 3.1 microg/L, P = .0001) compared to normal dogs (4.7 +/- 2.8 microg/L). Serum iron concentrations and total iron-binding capacity were significantly lower in dogs with lymphoma (110.8 +/- 56.7 microg/dL, P < .0001, and 236.6 +/- 45.6 microg/dL, P < .0001, respectively) and osteosarcoma (99.6 +/- 49.3 microg/dL, P < .0001, and 245.0 +/- 43.8 microg/dL, P = .0011, respectively) when compared to normal dogs (175.1 +/- 56.7 microg/dL and 277.1 +/- 47.4 microg/dL). Mean ferritin concentration was significantly higher in dogs with lymphoma (1291.7 +/- 63.0 microg/L) than in normal dogs (805.8 +/- 291.1 microg/L, P < .0001) and dogs with osteosarcoma (826.5 +/- 309.2 microg/L, P < .0001). Further investigation is needed to explore the clinical significance of these mineral abnormalities in dogs with cancer.     

吡啶甲酸铬对生长猪生产性能和组织中铬残留的影响

选用96头体重(24.67±0.36)kg,公母各半达兰猪,随机分为4组,每组4个重复,每个重复6头。对照组饲喂基础日粮,3个试验组分别添加200、400μg/kg和800μg/kg吡啶甲酸铬(以铬计)。另外,选用8头体重(24.98±0.56)kg达兰猪,随机分为2组,添加1600μg/kg和3200μg/kg吡啶甲酸铬(以铬计),试验期28d。结果表明,添加200～800μg/kg吡啶甲酸铬对猪平均日增重和饲料转化效率无显著影响(P>0.05),但可提高饲料采食量,800μg/kg处理组的采食量显著高于其他3个处理组(P=0.01)。添加200～3200μg/kg吡啶甲酸铬猪组织中铬残留量为0.08～0.35mg/kg。     

吡啶甲酸铬对饲喂不同脂肪水平日粮育肥猪胴体特性和胰岛素敏感性的影响

文章旨在研究不同脂肪水平日粮添加不同粒度吡啶甲酸铬对育肥猪生长性感、胴体特性及胰岛素敏感性的影响。试验选择平均体重为(51.8±3.45)kg的三元猪768头,试验采用2×4多因素方差设计,共2个脂肪水平(低脂和高脂),4个不同粒度吡啶甲酸铬水平(0 mg/kg,400 mg/kg粒度为320μm,15μm和50 nm的吡啶甲酸铬),其中每组4个重复,每个重复24头猪。试验共开展42 d。日粮添加吡啶甲酸铬较对照组显著提高了试验21 d肥猪的日增重(P<0.05);高脂日粮较低脂日粮显著提高了该阶段日增重(P<0.05)。日粮添加不同粒径吡啶甲酸铬显著提高了肥猪的屠宰率(P<0.05),吡啶甲酸铬组较对照组显著降低了背膘厚度(P<0.05);不同粒径吡啶甲酸铬显著提高了腰肌深度(P<0.05),吡啶甲酸铬和脂肪水平对腰肌深度的影响具有显著交互作用(P<0.05),其中添加吡啶甲酸铬的高脂日粮较其他组显著提高了腰肌深度(P<0.05)。日粮添加吡啶甲酸铬和脂肪水平对腰肌深度的影响具有显著交互作用(P<0.05),其中添加吡啶甲酸铬的高脂日粮较其他组显著提高了腰肌深度(P<0.05)。日粮添加吡啶甲酸铬显著降低了稳态模型(P<0.05),而高脂日粮显著提高了定量胰岛素敏感性检测指标(P<0.05)。综上所述:日粮添加吡啶甲酸铬可以提高育肥猪生长性能及胰岛素敏感性,其中微米和纳米级吡啶甲酸铬可以改善育肥猪胴体特性。     

Assessment of Insulin and Glucose Dynamics by Using an Oral Sugar Test in Horses

Straightforward testing procedures are needed to facilitate the diagnosis of insulin dysregulation in horses because hyperinsulinemia and insulin resistance are associated with laminitis. Results of an oral sugar test (OST) were compared with those of the intravenous glucose tolerance test (IVGTT). We hypothesized that OST and IVGTT area under the curve values for glucose (AUCg) and insulin (AUCi) would be closely correlated, as defined by a correlation coefficient value ≥0.90. Both tests were performed in 10 horses meeting the criteria for equine metabolic syndrome (EMS) and 8 Quarter horse crossbred mares from a university teaching herd (control group). The OST was also performed in 21 Quarter horse crossbred mares from the same herd, and test repeatability was evaluated in 8 of these horses. All testing was performed under fasting conditions. Median AUCg and AUCi values were 1.3- and 9.0-fold higher, respectively, for the IVGTT and 1.3- and 6.8-fold higher, respectively, for the OST in the EMS group than those in the control group. AUCg (Spearman correlation coefficient [r_s] = 0.58; P = .012) and AUCi (r_s = 0.90; P < .001) values for the two tests were positively correlated. Mean ± SD coefficients of variation for repeated tests in 8 mares were 6.4% ± 3.1% and 45.1% ± 36.2% for AUCg and AUCi, respectively. We conclude that OST and IVGTT insulin results are closely correlated, so the OST warrants further consideration as a field test for insulin dysregulation in horses.