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.     

Repeatability of 2 methods for assessment of insulin sensitivity and glucose dynamics in horses

Both the euglycemic-hyperinsulinemic clamp (EHC) and minimal model analysis of the frequently sampled intravenous glucose tolerance test (FSIGT) have been applied for measurement of insulin sensitivity in horses. However, no published data are available on the reproducibility of these methods. Therefore, the objective of this study was to evaluate the variation and repeatability of measures of glucose dynamics and insulin sensitivity in horses derived from minimal model analysis of the FSIGT and from the EHC method. Six healthy horses underwent both the FSIGT and EHC on 2 occasions over a 4-week period, with a minimum of 5 days between tests. Coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for measures of glucose metabolism and insulin sensitivity derived from each test. In the EHC, insulin sensitivity, expressed as the amount of metabolized glucose (M) per unit of serum insulin (I) (M/I ratio), averaged 0.19 +/- 0.06 x 10(-4) mmol/kg/min x (pmol/L)(-1) with an average interday CV of 14.1 +/- 5.7% (range, 7-20%) and ICC of 0.74. Minimal model analysis of the FSIGT demonstrated mean insulin sensitivity (Si) of 0.49 +/- 0.17 x 10(-4)/min x (pmol/L)(-1) with an average interday CV of 23.7 +/- 11.2% (range, 9-35%) and ICC of 0.33. Mean CV and ICC for minimal model glucose effectiveness (Sg) and acute insulin response (AIRg) were, respectively, 26.4 +/- 11.2% (range 13-40%) and 0.10 and 11.7 +/- 6.5% (range 7-21%) and 0.98. Insulin sensitivity measured by the EHC has lower interday variation when compared with the minimal model estimate derived from the FSIGT.     

Porcine somatotropin alters insulin response in growing pigs by reducing insulin sensitivity rather than changing responsiveness

Exogenous porcine somatotropin (pST) treatment consistently improves growth performance and reduces fat deposition in pigs, and it is hypothesized that one component of the mechanism is through altering the sensitivity and/or responsiveness to insulin. Therefore, a study was conducted to investigate the effect of pST treatment on whole-body glucose metabolism in response to varying doses of insulin. Eight barrows were surgically prepared with indwelling catheters and randomly assigned to one of two treatment groups (0 or 120 μg pST/kg BW · d) for 13 d. Whole-body glucose kinetics were measured during infusion of [6-(3)H]-glucose under basal conditions and during hyperinsulinemic-euglycemic clamps at various insulin infusion rates (7, 28, and 140, and 14, 70, and 280 ng insulin/kg BW · min) and alterations in the dose-response parameters were calculated with nonlinear regression. Treatment with pST increased basal plasma concentrations of glucose (36%; P = 0.005), insulin (276%; P = 0.001), and NEFAs (177%; P = 0.01) and decreased the rate of glucose disappearance (-59%; P = 0.001). The responsiveness (maximum response) for steady state glucose infusion rate to maintain glycemia was not altered by pST (112 vs 106 μmol/min · kg; P = 0.78), whereas the sensitivity (effective dose at 50% of maximum response) was increased almost 7-fold (1.3 vs 8.7 ng/mL; P = 0.027). Similar responses were observed for rate of glucose disappearance and insulin-dependent glucose utilization. Therefore, pST-induced insulin resistance with regard to whole-body glucose uptake is due to a reduced sensitivity to insulin, rather than a change in responsiveness.     

Calcium-stimulation test for the assessment of beta-cell function in cats

To assess the potential of an intravenous calcium-stimulation test (CST) as an indicator of insulin secretion in cats, indices calculated from CST results were compared with indices of insulin secretion derived from an intravenous glucose tolerance test (ivGTT) and hyperglycaemic glucose clamp (HGC) in 11 healthy, normal glucose tolerant, conscious cats. Intravenous administration of 2.5mg/kg Ca(2+) resulted in a significant increase in plasma free Ca(2+) (P<0.001) and plasma insulin (P=0.047) concentrations but did not affect the plasma glucose concentration. The indices of insulin secretion based on the CST did not correlate significantly with corresponding indices based on the ivGTT and HGC. In conclusion, the CST is not a useful test for assessing insulin secretion in cats. Other indices of insulin secretion, such as fasting insulin concentrations and the homeostasis model assessment of beta-cell function (HOMA-B), are easier to obtain and correlate better with indices of insulin secretion derived from the HGC, the gold standard technique for assessing insulin secretion.     

Comparison of Three Methods for Evaluation of Equine Insulin Regulation in Horses of Varied Body Condition Score

Multiple dynamic field tests are used for assessment of equine insulin resistance or altered insulin regulation. However, the relationship between markers of glucose homeostasis and insulin disposal obtained by different testing protocols is unknown. We hypothesized that two recently developed field tests for evaluation of equine insulin dysregulation, the insulin response to dexamethasone test (IRDT) and oral sugar test (OST), would yield comparable results to the hyperinsulinemic euglycemic clamp (HEC). Fifteen light breed horses with body condition scores (BCS) 3 of 9 to 8 of 9 were used in this study. Eight horses (BCS, 5 of 9 to 7 of 9) underwent an OST under two different housing conditions, pasture, and stall (experiment 1). These eight horses also underwent an HEC and IRDT over a 4-week period (experiment 2), and results were compared with the OST stall. Finally, eight horses (BCS, 3 of 9 to 8 of 9), including one horse from experiments 1 and 2, underwent an OST on pasture three times over a 14–16-week period during the summer and the fall (experiment 3). The HEC did not correlate with either the OST or IRDT. The OST was not different when performed in the pasture compared within a stall but did change significantly over time on pasture. These results suggest that in insulin-sensitive horses, the OST and IRDT results are not primarily determined by tissue insulin sensitivity in horses of varying BCS. Furthermore, OST results may vary depending on pasture composition or season.     

Effects of pentobarbitone anaesthesia and atropine on the intravenous glucose tolerance test in normal dogs

The effect of atropine (0·1 mg/kg b.w. s.c.) and of pentobarbitone anaesthesia (25 mg/kg b.w.) on the plasma glucose clearance and insulin response to an intravenous load of 600 mg and 1,250 mg/kg b.w. glucose was studied in twenty-four normal young Dalmatian dogs (ten male, fourteen female). Neither the rate of disappearance of glucose from the circulation, nor the insulin release following both glucose loads was altered by atropine. However, the disposal of intravenous glucose was significantly (P < 0·01) delayed and the insulin release significantly decreased under pentobarbitone anaesthesia. It is suggested that a decreased blood flow through the pancreas during pentobarbitone anaesthesia is most likely the cause of the decreased insulin release which in turn causes a delayed rate of disappearance of glucose from the circulation. It is therefore concluded that an intravenous glucose tolerance test, as diagnostic procedure, should never be done in anaesthetized dogs.     

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.     

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.     

Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies

The purpose of this study was to determine the effects of prolonged administration of insulin, whilst maintaining normal glucose concentrations, on hoof lamellar integrity in vivo on healthy ponies with no known history of laminitis or insulin resistance. Nine clinically healthy, unrelated ponies were randomly allocated to either a treatment group (n =5; 5.9+/-1.7 years) or control group (n =4; 7.0+/-2.8 years). The treatment group received insulin via a euglycaemic hyperinsulinaemic clamp technique modified and prolonged for up to 72 h. Control ponies were infused with an equivalent volume of 0.9% saline. Ponies were euthanized at the Obel grade 2 stage of clinical laminitis and hoof lamellar tissues were harvested and examined for histopathological evidence of laminitis. Basal serum insulin and blood glucose concentrations were 15.7+/-1.8 microU/mL and 5.2+/-0.1 mmol/L, respectively (mean+/-SE) and were not significantly different between groups. Mean serum insulin concentration in treatment ponies was 1036+/-55 microU/mL vs. 14.6 microU/mL in controls. All ponies in the treatment group developed clinical and histological laminitis (Obel grade 2) in all four feet within 72 h (55.4+/-5.5h), whereas none of the control ponies developed laminitis. There was no clinical evidence of gastrointestinal involvement and the ponies showed no signs of systemic illness throughout the experiment. The data show that laminitis can be induced in healthy young ponies, with no prior history of laminitis, by maintaining prolonged hyperinsulinaemia with euglycaemia. This suggests a role for insulin in the pathogenesis of laminitis, independent of hyperglycaemia, or alterations in hind-gut fermentation. For the clinician, early detection and control of hyperinsulinaemia may facilitate management of endocrinopathic laminitis.     

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.     

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.     

Acute phase proteins response in cats naturally infected by hemotropic mycoplasmas

Information about the acute phase proteins (APP) response in cats naturally infected with hemoplasmas and in cats co-infected with different species of hemoplasmas is lacking.This study evaluated serum amyloid A (SAA), haptoglobin (Hp) and albumin in 48 cats naturally infected with hemoplasmas, including 25 with Candidatus Mycoplasma haemominutum and 23 co-infected with different hemoplasmas agents; and in 10 healthy control cats.Infected cats had significantly higher Hp and lower albumin than controls. Symptomatic cats had significantly higher SAA and Hp, and lower albumin than asymptomatic animals, and also than controls. Asymptomatic cats had significantly higher Hp than controls. Concentrations of APP were not significantly different between single infected and co-infected cats.According with these results, hemoplasmosis should be considered when alterations in APP are detected in diseased cats with compatible clinical signs. Furthermore, a subclinical infection should be considered in apparently healthy cats from endemic areas with increased Hp.     

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.     

Glucose and insulin responses to different dietary energy sources in Thoroughbred broodmares grazing cool season pasture

The objectives of this study were to characterize the glycemic and insulinemic responses of Thoroughbred broodmares fed late spring pasture only or a mixture of pasture and a high starch or low starch feed and to test hypotheses about differences in the glycemic and insulinemic effects of these dietary regimes. A group of 15 mares were divided into three treatment groups; pasture and high starch feed (PHS), pasture and low starch feed (PLS), and pasture only (PO) and maintained in these groups for 4.5 months prior to this study. These groups were maintained on a single pasture that was temporarily divided into three sections. The study protocol was conducted over two days. On day 1 the mares were fed their respective treatments and on day 2 all mares were allowed access to pasture only. On both days plasma glucose and insulin were measured in samples taken over a 7.5 h period. Baseline measurements for glucose and insulin were not different between any of the treatment groups on either day (P > 0.05). The baseline insulin concentrations of these pasture-kept mares (26.7 ± 8.3 mIU/L) were high compared to those reported from stall-kept horses. Plasma glucose and insulin on day 1 were influenced by treatment group, sample time, and an interaction between treatment and time (P < 0.05). On day 2 there was no significant influence of treatment group (P > 0.05). Glucose and insulin rose to higher (P < 0.01) peak concentrations in the PHS group on day 1 when compared to the PLS and PO groups, with no difference (P > 0.05) detected between the PLS and PO groups. These results are reflected in greater areas under the concentration-time curves for glucose and insulin in the PHS group on day 1 (P < 0.05). On day 2 there were no differences in any of the glucose and insulin characteristics for any of the treatment groups (P > 0.05). These results indicate a clear difference in the glycemic and insulinemic effect of the PHS feed compared to the PLS and PO groups. Of further interest are the glucose and insulin characteristics of these pasture-kept mares that indicate a low insulin sensitivity and high insulin secretory response. This study provides further information on factors influencing glycemic and insulinemic responses in horses.     

Remission of diabetes mellitus in cats cannot be predicted by the arginine stimulation test

Background: Cats with diabetes mellitus frequently achieve clinical remission, suggesting residual β‐cell function. Responsiveness of β‐cells to arginine persists the longest during diabetes progression, making the intravenous arginine stimulation test (IVAST) a useful tool to assess residual insulin and glucagon secretion. Hypothesis: Diabetic cats with and without remission will have different arginine‐induced insulin or glucagon response. Animals: Seventeen cats with diabetes, 7 healthy cats. Methods: Blood samples collected on admission and during subsequent IVAST. Glucose, insulin, and glucagon were measured. Response to IVAST was assessed by calculating the insulin and glucagon area under the curve (AUC) and the AUC glucagon‐to‐insulin ratio. Diabetic cats were treated with insulin and were followed for 18 weeks. Remission was defined as normoglycemia and disappearance of clinical signs of diabetes for ≥4 weeks, without requiring insulin. Results: Seven diabetic cats (41%) achieved remission. On admission, blood glucose concentration was significantly lower in cats with remission (median, 389 mg/dL; range, 342–536 mg/dL) than in those without remission (median, 506 mg/dL; range, 266–738 mg/dL). After IVAST, diabetic cats with remission had higher AUC glucagon‐to‐insulin ratios (median, 61; range, 34–852) than did cats without remission (median, 26; range, 20–498); glucose, insulin, and glucagon AUCs were not different. Diabetic cats had lower insulin AUC than did healthy cats but comparable glucagon AUC. Conclusions and Clinical Importance: Diabetic cats with and without remission have similar arginine‐stimulated insulin secretion on admission. Although cats with remission had lower blood glucose concentrations and higher AUC glucagon‐to‐insulin ratios, large overlap between groups prevents use of these parameters in clinical practice.     

Decreased gene expression of insulin signaling genes in insulin sensitive tissues of obese cats

Type 2 diabetes mellitus (DM) animal models have provided ample opportunity for investigating pathogenesis, as well as to evaluate novel treatment and prevention options for the disease. Because the domestic cat shares a similar environment with humans, it is also confronted with many similar risk factors for diabetes, such as physical inactivity and obesity. Obesity is a significant risk factor for diabetes in cats, and as such, the domestic cat may serve as an ideal model for investigating obesity induced insulin resistance. This study determined changes in insulin signaling genes within insulin sensitive tissues of obese felines. Quantitative RT-PCR was performed to determine mRNA levels of three important insulin signaling genes which have been implicated with insulin resistance: insulin receptor substrate (IRS)-1, IRS-2, and phosphatidylinositol 3’-kinase (PI3-K) p85α. Obese cats had significantly lower IRS-2 and PI3-K p85α mRNA levels in liver and skeletal muscle as compared to control cats. This down regulation of insulin signaling genes in obese cats mirrors that of obese humans and rodents suffering from insulin resistance. Interestingly, preprandial blood tests indicated that our obese cats were no different from control cats with regards to glucose tolerance and insulin resistance, thus indicating that the obese cats used in our study had a moderate level of obesity. Therefore, insulin signaling gene alterations were occurring in insulin sensitive tissues of moderately obese felines before glucose intolerance was clinically evident. As such, the monitoring of key insulin signaling genes may have some important diagnostic value to determine the risk level and degree of obesity induced insulin resistance.     

Pancreatic insulin release and peripheral insulin sensitivity in German black headed mutton and Finish Landrace ewes: evaluation of the role of insulin resistance in the susceptibility to ovine pregnancy toxemia

German black headed mutton (GBM) ewes are recognized as being highly susceptible to ovine pregnancy toxemia (OPT). The present trial was performed to evaluate whether a breed-dependent gestational diabetes mellitus-like insulin resistance during late pregnancy might be responsible for the high incidence of OPT in the GBM breed. Modified frequently sampled intravenous glucose tolerance tests (300 mg glucose and 0.03 IU insulin per kg of BW) were performed during mid and late pregnancy, the periparturient, and the dry period in polytocous 3.5-yr-old GBM and Finnish Landrace (FL) ewes fed according to their requirements. The corresponding blood samples were analyzed for plasma concentrations of glucose, insulin, nonesterified fatty acids (NEFAs) and β-hydroxybutyrate (β-HB). In addition, the baseline plasma cortisol concentrations were determined during late pregnancy. The BW gain during pregnancy and the rearing success did not differ between the GBM and FL ewes. In both breeds, late pregnancy was associated with decreased basal plasma glucose concentrations and enhanced glucose disposal, as well as elevated baseline β-HB values. Only in the GBM ewes did the plasma NEFA concentrations increase significantly during advancing pregnancy. Moreover, significantly higher baseline plasma NEFA concentrations as well as lower (P < 0.05) basal plasma glucose values were recorded during late pregnancy in the GBM than in the FL ewes. The first-phase insulin secretion, the peripheral insulin sensitivity, and the baseline plasma cortisol values did not differ between both breeds during late pregnancy. It is concluded that increased lipolysis during late pregnancy is a characteristic of the GBM breed. Moreover, elevated plasma NEFA concentrations may contribute to impaired pancreatic insulin response and peripheral insulin resistance in GBM ewes and thus promote OPT.     

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.