Objective—To compare beta-cell sensitivity to glucose, first-phase insulin secretion, and glucose tolerance between dogs with naturally occurring obesity of > 2 years' duration and lean dogs.
Animals—17 client-owned obese or lean dogs.
Procedures—Frequently sampled IV glucose tolerance tests were performed with minimal model analysis on 6 obese dogs and matched controls. Glucagon stimulation tests were performed on 5 obese dogs and matched controls.
Results—Obese dogs were half as sensitive to the effects of insulin as lean dogs. Plasma glucose concentrations after food withholding did not differ significantly between groups; plasma insulin concentrations were 3 to 4 times as great in obese as in lean dogs. Obese dogs had plasma insulin concentrations twice those of lean dogs after administration of glucose and 4 times as great after administration of glucagon. First-phase insulin secretion was greater in obese dogs.
Conclusions and Clinical Relevance—Obese dogs compensated for obesity-induced insulin resistance by secreting more insulin. First-phase insulin secretion and beta-cell glucose sensitivity were not lost despite years of obesity-induced insulin resistance and compensatory hyperinsulinemia. These findings help explain why dogs, unlike cats and humans, have not been documented to develop type 2 diabetes mellitus.
Objective—To evaluate the effects of oral administration of anti-inflammatory dosages of prednisone for 28 days on serum aldosterone, cortisol, and electrolyte concentrations in clinically normal dogs.
Procedures—On days 1 through 28, 5 dogs received prednisone (0.55 mg/kg, PO, q 12 h) and 5 dogs received similar treatments with a placebo (empty capsules). Serum cortisol and aldosterone concentrations before and after ACTH stimulation testing and serum electrolyte concentrations were measured before (day 0 [baseline]), during (days 7, 14, 21, and 28), and after (days 35 and 42) treatment.
Results—At baseline, variables did not differ between the 2 groups. Serum cortisol concentrations before and after ACTH stimulation testing did not change from baseline values in placebo-treated dogs. In prednisone-treated dogs, serum chloride and corrected chloride concentrations were significantly lower on days 7, 14, 21, and 28 and serum bicarbonate concentrations were significantly higher on days 14, 21, and 28, compared with baseline values. Serum cortisol concentrations before and after ACTH stimulation testing were significantly lower than baseline values during prednisone treatment. Serum aldosterone concentration after ACTH stimulation testing was significantly lower than baseline on day 35 (ie, 1 week after discontinuation of prednisone treatment) but returned to baseline by day 42 in prednisone-treated dogs.
Conclusions and Clinical Relevance—Administration of anti-inflammatory dosages of prednisone caused significant changes in serum chloride, bicarbonate, and cortisol concentrations in clinically normal dogs. Although ACTH-stimulated serum aldosterone concentrations were unchanged from baseline during glucocorticoid administration, values decreased after treatment cessation but quickly returned to baseline values.
Objective—To evaluate alterations in ligand-stimulated activity of G proteins in thyroid gland cells of hyperthyroid cats.
Sample Population—Membranes of thyroid gland cells isolated from 5 hyperthyroid cats and 3 age-matched euthyroid (control) cats immediately after the cats were euthanatized.
Procedures—Isolated thyroid cell membranes were treated with thyroid-stimulating hormone (TSH), and activation of G protein was quantified by measurement of the binding of guanosine triphosphate γ labeled with sulfur 35 (GTPγ35S). The separate effects of G-protein inhibitory (Gi) and G-protein stimulatory (Gs) proteins were determined by the use of pertussis toxin and cholera toxin, respectively.
Results—Thyroid cell membranes from hyperthyroid cats had higher basal GTPγ35S binding than did thyroid cell membranes from euthyroid cats. Thyroid cell membranes from hyperthyroid and euthyroid cats had a concentration-dependent increase in TSH-stimulated GTPγ35S binding over the TSH range of 0 to 100 mU/mL, with maximal activity at 1 to 100 mU/mL for both. The percentage increase in GTPγ35S binding stimulated by TSH was similar in magnitude between the membranes from hyperthyroid and euthyroid cats. The TSH-stimulated activation of Gs and Gi was not different between euthyroid and hyperthyroid cats.
Conclusions and Clinical Relevance—Ligand-stimulated activation of G proteins was the same in thyroid cell membranes obtained from hyperthyroid and euthyroid cats. Therefore, alterations in inherent Gs or Gi activities did not appear to be part of the pathogenesis of hyperthyroidism in cats.
Objective—To determine effects of exercise training without dietary restriction on adiposity, basal hormone and lipid concentrations and glucose and insulin dynamics in overweight or obese, insulin-resistant horses.
Animals—12 overweight or obese (body condition score ≥ 7), insulin-resistant (insulin sensitivity ≤ 1.2 × 10−4 L/min/mU) geldings.
Procedures—4 horses remained sedentary, and 8 horses were exercised for 4 weeks at low intensity and 4 weeks at higher intensity, followed by 2 weeks of detraining. Prior to and after each training period, frequently sampled IV glucose tolerance tests with minimal model analysis were performed and baseline plasma insulin, glucose, triglycerides, non-esterified fatty acids, and leptin concentrations were analyzed. Adiposity was assessed by use of morphometrics, ultrasonic subcutaneous fat thickness, and estimation of fat mass from total body water (deuterium dilution method).
Results—Body weight and fat mass decreased by 4% (mean ± SD, 20 ± 8 kg) and 34% (32 ± 9 kg), respectively, compared with pre-exercise values, with similar losses during low- and higher-intensity training. There was no effect of exercise training on subcutaneous fat thickness, plasma hormone and lipid concentrations, or minimal model parameters of glucose and insulin dynamics.
Conclusions and Clinical Relevance—Results suggested that moderate exercise training without concurrent dietary restriction does not mitigate insulin resistance in overweight or obese horses. A more pronounced reduction in adiposity or higher volume or intensity of exercise may be necessary for improvement in insulin sensitivity in such horses.
Objective—To investigate the effects of dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics.
Procedures—Horses were randomly allocated to 3 treatment groups and received 48 mg of levothyroxine mixed with 200 g of oats, 20 mg of dexamethasone plus oats, or oats alone (control) for 15 days, followed by IV infusion of lipopolysaccharide (20 ng/kg) while individually housed in stalls. Frequently sampled IV glucose tolerance tests were performed prior to pretreatment, after pretreatment, and 20 hours after lipopolysaccharide administration. Area under the curve for plasma glucose and serum insulin concentrations was calculated, and minimal model analyses were performed.
Results—Significant treatment-by-time effects were detected for insulin sensitivity (SI) and area under the curve for glucose and insulin in the 15-day pretreatment period. Insulin sensitivity significantly decreased over time in all treatment groups, with the largest decrease detected in the dexamethasone group. Administration of lipopolysaccharide further decreased mean SI by 71% and 63% in the dexamethasone and control groups, respectively, but did not affect horses in the levothyroxine group. Mean SI was the lowest in the dexamethasone group, but percentage reduction was the same for dexamethasone and control groups.
Conclusions and Clinical Relevance—Insulin sensitivity decreased during the pretreatment period in all 3 groups, indicating that hospitalization affected glucose and insulin dynamics. Dexamethasone significantly lowered SI, and endotoxemia further exacerbated insulin resistance. In contrast, there was no additional effect of endotoxemia on SI in horses pretreated with levothyroxine, suggesting that this treatment prevented endotoxemia-induced insulin resistance.
Objective—To determine the effects of diet-induced weight gain on glucose and insulin dynamics and plasma hormone and lipid concentrations in horses.
Animals—13 adult geldings.
Procedures—Horses were fed 200% of their digestible energy requirements for maintenance for 16 weeks to induce weight gain. Frequently sampled IV glucose tolerance tests were performed before and after weight gain to evaluate glucose and insulin dynamics. Adiposity (assessed via condition scoring, morphometric measurements, and subcutaneous fat depth) and plasma concentrations of insulin, glucose, nonesterified fatty acids, triglycerides, and leptin were measured on a weekly or biweekly basis.
Results—Mean ± SD body weight increased by 20% from 440 ± 44 kg to 526 ± 53 kg, and body condition score (scale, 1 to 9) increased from 6 ± 1to8 ± 1. Plasma glucose, triglyceride, and nonesterified fatty acid concentrations were similar before and after weight gain. Leptin and insulin concentrations increased with weight gain. Mean ± SD insulin sensitivity decreased by 71 ± 28%, accompanied by a 408 ± 201% increase in acute insulin response to glucose, which resulted in similar disposition index before and after weight gain.
Conclusions and Clinical Relevance—Diet-induced weight gain in horses occurred concurrently with decreased insulin sensitivity that was effectively compensated for by an increase in insulin secretory response. Obesity resulted in hyperinsulinemia and hyperleptinemia, compared with baseline values, but no changes in lipid concentrations were apparent. Preventing obesity is a potential strategy to help avoid insulin resistance, hyperinsulinemia, and hyperleptinemia in horses.
Objective—To study the effects of experimentally induced hypothyroidism on skeletal muscle and characterize any observed myopathic abnormalities in dogs.
Animals—9 female, adult mixed-breed dogs; 6 with hypothyroidism induced with irradiation with 131 iodine and 3 untreated control dogs.
Procedures—Clinical examinations were performed monthly. Electromyographic examinations; measurement of plasma creatine kinase, alanine aminotransferase, aspartate aminotransferase, lactate, and lactate dehydrogenase isoenzyme activities; and skeletal muscle morphologic-morphometric examinations were performed prior to and every 6 months for 18 months after induction of hypothyroidism. Baseline, 6-month, and 18-month assessments of plasma, urine, and skeletal muscle carnitine concentrations were also performed.
Results—Hypothyroid dogs developed electromyographic and morphologic evidence of myopathy by 6 months after treatment, which persisted throughout the study, although these changes were subclinical at all times. Hypothyroid myopathy was associated with significant increases in plasma creatine kinase, aspartate aminotransferase, and lactate dehydrogenase 5 isoenzyme activities and was characterized by nemaline rod inclusions, substantial and progressive predominance of type I myofibers, decrease in mean type II fiber area, subsarcolemmal accumulations of abnormal mitochondria, and myofiber degeneration. Chronic hypothyroidism was associated with substantial depletion in skeletal muscle free carnitine.
Conclusions and Clinical Relevance—Chronic, experimentally induced hypothyroidism resulted in substantial but subclinical phenotypic myopathic changes indicative of altered muscle energy metabolism and depletion of skeletal muscle carnitine. These abnormalities may contribute to nonspecific clinical signs, such as lethargy and exercise intolerance, often reported in hypothyroid dogs.
Objective—To partially characterize the cDNA, amino acid sequence, and tertiary structure of feline myeloperoxidase, describe its cellular location in mature granulocytes, and determine whether hyperthyroid cats have anti-myeloperoxidase antibody.
Sample Population—Bone marrow RNA and whole blood from cats of various sources and feline serum samples submitted for measurement of total thyroxine concentration from September 2006 to July 2007.
Procedures—Feline myeloperoxidase cDNA was amplified from bone marrow RNA; presumptive splice sites were determined by comparison with human sequences. Intracellular localization of myeloperoxidase in granulocytes was determined by use of immunofluorescence and electron microscopy, and molecular weight and partial tertiary structure were determined by use of immunoblotting of granulocyte lysates. Anti-human myeloperoxidase (hMPO) antibody was detected via ELISA.
Results—A 2,493-bp sequence encompassing the 2,160-bp cDNA with presumably the same number and size of exons as hMPO was generated. Translation predicted 85% homology with hMPO. Feline myeloperoxidase was localized to neutrophil primary granules, and immunoblotting revealed heavy and light bands with molecular weights similar to those of hMPO. The prevalence of anti-hMPO antibody did not differ between nonhyperthyroid and hyperthyroid cats or among hyperthyroid cats subclassified by treatment modality.
Conclusions and Clinical Relevance—Moderate homology existed between feline myeloperoxidase and hMPO cDNA and protein. Although findings suggested a similar tertiary structure and function for the 2 proteins, they also suggested that inability to detect a high prevalence of anti-hMPO antibody in hyperthyroid cats may be attributable to antigenic differences between the human and feline proteins rather than a lack of autoantibody.
Objective—To compare concentrations of urinary iodide (UI) in euthyroid and untreated hyperthyroid cats.
Animals—118 euthyroid and 88 hyperthyroid client-owned cats from 2 nonreferral veterinary practices.
Procedures—Iodide concentration was measured in 5 urine samples collected every 3 to 12 months from selected cats, and variability of results between euthyroid cats and hyperthyroid cats prior to the diagnosis of hyperthyroidism was evaluated via 1-way ANOVA, after logarithmic transformation of UI concentrations (logUIs). The UI concentration in hyperthyroid cats was measured at diagnosis and 2 to 6 weeks and 3 to 6 months after treatment for hyperthyroidism. The pretreatment logUI in hyperthyroid cats was compared with that in euthyroid cats, taking into account the effects of renal function on UI concentration. Iodine intake was estimated in euthyroid cats following calculation of the volume of daily urine output, with a fixed value for iodine concentration in feces.
Results—The variability of UI concentrations did not differ significantly between hyperthyroid (n = 10) and euthyroid (8) cats. The logUI increased 2 to 6 weeks after initiation of treatment in hyperthyroid cats (n = 80) and was lower in azotemic versus nonazotemic cats. Hyperthyroid cats had a lower logUI than euthyroid cats, and there was no evidence of deficient iodine intake in euthyroid cats.
Conclusions and Clinical Relevance—The logUI was lower in cats with azotemia and with untreated hyperthyroidism, compared with that in euthyroid cats from the same population. Additional studies are needed to determine whether iodine intake plays a role in the development of hyperthyroidism in cats.
Objective—To determine whether results of cytologic evaluation of preputial epithelial cells correspond to results of a serum endocrine hormone assay and clinical signs associated with adrenocortical disease in castrated ferrets.
Animals—13 clinically normal ferrets and 8 ferrets with signs of adrenocortical disease.
Procedures—Blood and preputial lavage samples were collected from each ferret. Serum samples were submitted to the University of Tennessee Veterinary Diagnostic Laboratory for performance of an endocrine hormone assay. Differential epithelial cell counts were performed on preputial lavage samples to determine the percentage of cornified cells. Results of cytologic evaluation were compared with results of the endocrine hormone assay and clinical status of ferrets.
Results—The percentage of cornified preputial epithelial cells was not significantly correlated with serum 17B-estradiol or androstenedione concentration but was significantly correlated with serum 17-hydroxyprogesterone concentration (r = 0.60). The percentage of cornified preputial epithelial cells was higher in ferrets with clinical signs of adrenocortical disease (mean ± SD, 71.3 ± 16.9%) than in clinically normal ferrets (55.5 ± 19.0%).
Conclusions and Clinical Relevance—Cornification of preputial epithelial cells was correlated with an increase in serum 17-hydroxyprogesterone concentration as well as clinical signs of adrenocortical disease in castrated ferrets. Additional investigation is needed to elucidate the mechanism of preputial epithelial cell cornification in castrated ferrets.