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 the effects of dexamethasone or synthetic ACTH administration on endogenous ACTH concentrations in healthy dogs.
Animals—10 healthy neutered dogs.
Procedures—Each dog received dexamethasone (0.01 mg/kg), synthetic ACTH (5 μg/kg), or saline (0.9% NaCl) solution (0.5 mL) IV at intervals of ≥ 30 days. Plasma endogenous ACTH concentrations were measured before (baseline; time 0) and 1, 8, 12, and 24 hours after drug administration; serum cortisol concentrations were measured before and 1 hour after synthetic ACTH and saline solution administration and 8 hours after dexamethasone administration.
Results—Analysis of serum cortisol concentrations confirmed effects of drug administration. Dexamethasone significantly decreased the endogenous ACTH concentration from the baseline value at both 8 and 12 hours. Synthetic ACTH administration significantly decreased the endogenous ACTH concentration from the baseline value at 8 hours. Saline solution administration had no significant effect on endogenous ACTH concentration.
Conclusions and Clinical Relevance—Dexamethasone and synthetic ACTH administered IV at doses used routinely during testing for hyperadrenocorticism caused significant but transient reductions of endogenous ACTH concentrations in healthy dogs. Thus, a 2-hour washout period following ACTH stimulation testing before collection of samples for measurement of the endogenous ACTH concentration may be insufficient. Although this effect has not been verified in dogs with hyperadrenocorticism, these data suggested that samples for measurement of endogenous ACTH concentrations should be obtained before or > 8 hours after initiation of an ACTH stimulation test or before or > 12 hours after the start of a low-dose dexamethasone suppression test.
Objective—To determine whether expression of G
proteins (Gi and Gs) is altered in thyroid gland adenomas
obtained from hyperthyroid cats.
Sample Population—Adenomatous thyroid glands
obtained from 8 hyperthyroid cats and thyroid glands
obtained from 4 age-matched euthyroid cats.
Procedure—Expression of Gi and Gs was quantified
in enriched membrane preparations of thyroid gland
tissue, using immunoblotting with Gi and Gs antibodies
and toxin-catalyzed ADP-ribosylation.
Results—Expression of Gi was significantly reduced
in thyroid gland adenomas from hyperthyroid cats,
compared with normal thyroid gland tissue from
euthyroid cats. Expression of Gs was similar between
the 2 groups.
Conclusions and Clinical Relevance—A decrease in
expression of Gi in adenomatous thyroid glands of
cats may reduce the negative inhibition of the cAMP
cascade in thyroid cells, leading to autonomous
growth and hypersecretion of thyroxine.
Understanding the molecular mechanisms for hyperthyroidism
in cats may lead to better treatment or,
ultimately, prevention of the disease. (Am J Vet Res
Objective—To evaluate glycemic response to insulin
treatment in dogs with diabetes mellitus.
Animals—221 dogs with diabetes mellitus.
Procedure—Type and dosage of insulin used, minimum
and maximum blood glucose concentrations,
time of blood glucose concentration nadir, and optimal
duration of action of insulin were determined on
the basis of data obtained prior to initial examination
at the teaching hospital (127 dogs), at the time of initial
examination (212 dogs), at the time a second follow-
up blood glucose curve was performed (59 dogs),
and at the time of clinical control of diabetes mellitus
Results—Prior to examination, 69 of 127 dogs (54%)
received 1 SC insulin injection daily. Thirty-one dogs
(24%) received a high dose of insulin (ie, > 1.5 U/kg
[0.7 U/lb] of body weight); 27 of these dogs (87%)
received 1 injection/d. Eleven of 16 dogs (69%) that
were hypoglycemic (blood glucose concentration
< 80 mg/dl) also received 1 injection/d. However, optimal
duration of action of insulin was > 12 hours in
only 5 of 83 dogs (6%) evaluated at the time diabetes
mellitus was clinically controlled. At that time, only 1
dog (1%) received a high dose of insulin, and the dog
received 2 injections/d. Moreover, 8 of 10 dogs (80%)
with hypoglycemia received 1 injection/d.
Conclusions and Clinical Relevance—Most dogs
with diabetes mellitus are clinically regulated with 2
daily insulin injections. Administration of a high dose
of insulin or development of hypoglycemia may be
more common in diabetic dogs that receive insulin
once daily, compared with dogs that receive insulin
twice daily. ( J Am Vet Med Assoc 2000;216:217–221)
Objective—To identify within guanosine triphosphate–binding proteins (G proteins) the subset of
inhibitory G proteins (Gi) that have decreased expression
in adenomatous thyroid glands obtained from
Sample Population—Adenomatous thyroid glands
obtained from 5 hyperthyroid cats and normal thyroid
glands obtained from 3 age-matched euthyroid cats.
Procedure—Expression of Gi1, Gi2, and Gi3 in
enriched membrane preparations from thyroid glands
was quantified by use of immunoblotting with Gi subtype-specific antibodies.
Results—Expression of Gi2 was significantly
decreased in tissues of hyperthyroid glands, compared
with expression in normal thyroid tissue.
Expression of Gi1 and Gi3 was not significantly different
between normal thyroid tissues and tissues from
Conclusions and Clinical Relevance—A decrease in
Gi2 expression decreases inhibition of adenylyl
cyclase and allows a relative increase in stimulatory G
protein expression. This results in increased amounts
of cAMP and subsequent unregulated mitogenesis
and hormone production in hyperthyroid cells.
Decreased Gi2 expression may explain excessive
growth and function of the thyroid gland in cats with
hyperthyroidism. (Am J Vet Res 2005;66:1478–1482)
Objective—To determine which dog breeds are at low
and high risk for developing diabetes mellitus (DM).
Animals—Hospital population of 221 dogs with DM
and 42,882 dogs without DM during 5.5 years.
Procedure—165 breeds (including a mixed-breed category)
were represented in the hospital population.
Breed-specific expected numbers of dogs with DM
were calculated by multiplying the proportion of all
dogs admitted to the hospital that were determined
to have DM during the study period by the breed-specific
totals during the study period. Breeds or breed
groups evaluated in the analysis (n = 20) were restricted
to those that had a combined observed and
expected count > 5 to document breeds at low and
high risk for developing DM. Proportionate changes in
the risk of developing DM by breed were calculated
and presented using exact odds ratios, 95% confidence
intervals, and P values. Mixed-breed dogs
were chosen as the reference breed.
Results—Samoyeds, Miniature Schnauzers, Miniature
Poodles, Pugs, and Toy Poodles were at high risk
for developing DM. Dog breeds found to be at low
risk for developing DM were German Shepherd Dog,
Golden Retriever, and American Pit Bull Terrier.
Conclusion and Clinical Relevance—The finding
that certain dog breeds are at low or high risk for
developing DM suggests that some genetic defects
may predispose dogs to development of DM, whereas
other genetic factors may protect dogs from development
of DM. (J Am Vet Med Assoc 2000;216:
Animals—7 dogs with well-regulated naturally occurring
insulin-dependent diabetes mellitus.
Procedure—Dogs were fed 1 of 3 diets for 1 month
each in 1 of 6 randomized diet sequences. Diets
included a low-fiber diet (LF) and 2 high-fiber diets; 1
contained only insoluble fiber (HIF), and 1 contained
soluble fiber in addition to insoluble fiber (HSF).
Caloric intake was unchanged throughout the study.
Glycemic control was assessed after each feeding
trial by measuring serum fructosamine concentration
and performing 5 serial measurements of blood glucose
concentration every 2 hours after the morning
feeding and insulin injection.
Results—Significant differences were not detected in
body weight, required insulin dosage, or albumin concentration
among dogs fed the HIF, HSF, and LF diets.
Mean and maximum blood glucose concentrations
and area under the blood glucose curve were significantly
lower in dogs fed the HIF diet, compared with
values in the same dogs fed the HSF or LF diet.
Fructosamine concentration was significantly lower in
dogs fed the HIF or HSF diet, compared with values
in the same dogs fed the LF diet.
Conclusions and Clinical Relevance—In dogs with
naturally occurring insulin-dependent diabetes mellitus,
a dry, high insoluble-fiber diet may aid in glycemic
control. (J Am Vet Med Assoc 2000;216:1076–1081)
Objective—To characterize concurrent disorders in
dogs with diabetes mellitus (DM).
Animals—221 dogs with DM.
Procedure—Medical records were reviewed, and
clinical signs, physical examination findings, and
results of clinicopathologic testing, urinalysis, aerobic
bacterial culture of urine samples, coagulation testing,
endocrine testing, histologic evaluation, diagnostic
imaging, and necropsy were recorded.
Results—For most dogs, CBC results were normal.
Common serum biochemical abnormalities included
hypochloremia (127 dogs, 60%) and high alanine
aminotransferase (163, 78%), aspartate aminotransferase
(78, 71%), and alkaline phosphatase (188,
90%) activities. Venous pH and serum ionized calcium
concentration were measured in 121 and 87 dogs,
respectively, and were low in 56 (46%) and 41 (47%)
dogs. Lipemia was observed in 92 (42%) dogs. Urine
samples from 159 (72%) dogs were submitted for
aerobic bacterial culture, and 34 (21%) yielded bacterial
growth. Escherichia coli was the most commonly
isolated organism. Thirty-six (16%) dogs had dermatitis
or otitis. Hyperadrenocorticism was diagnosed in
51 (23%) dogs on the basis of clinical signs and
results of a low-dose dexamethasone suppression
test (41 dogs), an adrenocorticotropic hormone stimulation
test (5), both tests (4), or histologic evaluation
of necropsy specimens (1). Acute pancreatitis was
diagnosed in 28 (13%) dogs. Eleven (5%) dogs had
tumors for which a histologic diagnosis was obtained.
Eight (4%) dogs were hypothyroid.
Conclusions and Clinical Relevance—Results suggest
that dogs with diabetes mellitus may have many
concurrent disorders. The most commonly identified
concurrent disorders included hyperadrenocorticism,
urinary tract infection, dermatitis, otitis, acute pancreatitis,
neoplasia, and hypothyroidism. (J Am Vet Med