Erythrocyte insulin receptors in dogs with spontaneous hyperadrenocorticism

Erythrocyte insulin receptor binding measurements were evaluated in 8 dogs with spontaneous hyperadrenocorticism. These dogs had normal serum glucose concentration, with normal to high serum insulin concentration (range, 45 to 1,400 pmol/L; normal, 40 to 170 pmol/L). Dogs with hyperadrenocorticism had significant (P less than 0.01) decrease in mean +/- SEM percentage of maximal binding for erythrocyte insulin receptors (2.25 +/- 0.21%), compared with results in 11 clinically normal pet dogs (4.29 +/- 0.42%). The decrease in erythrocyte receptor binding was attributed to significant (P less than 0.01) decrease in high-affinity receptor sites in dogs with hyperadrenocorticism (14.5 +/- 2.8), compared with clinically normal dogs (31.2 +/- 4.3). Significant differences in receptor affinity were not apparent between the 2 groups. Percentage of maximal binding for erythrocyte insulin receptors for dogs with hyperadrenocorticism was inversely correlated with serum insulin concentration (r = -0.85, P less than 0.01). Results indicate that the observed decrease in erythrocyte insulin receptor binding could contribute to insulin resistance and hyperinsulinemia associated with hyperadrenocorticism. Alternatively, decreased binding of insulin receptors in animals with hyperadrenocorticism may result from down-regulation secondary to hyperinsulinemia itself caused by insulin resistance at a postreceptor site (decreased responsiveness).     

Effect of a single dose of dexamethasone on glucose homeostasis in healthy horses by using the combined intravenous glucose and insulin test

Sustained dexamethasone administration to horses results in insulin resistance, which may predispose them to laminitis. A single dose of dexamethasone is commonly used as a diagnostic aid, yet the effect of a single dose of dexamethasone on glucose homeostasis in horses is not well defined. The objective of this study was to characterize the change in glucose dynamics over time in response to a single dose of dexamethasone. A combined glucose-insulin tolerance test (CGIT) was performed on 6 adult geldings before and at 2, 24, and 72 h postdexamethasone (40 microg/kg of BW, i.v.); a minimum of 1 wk of rest was allowed between treatments. Before any treatment, the CGIT resulted in a hyperglycemic phase followed by a hypoglycemic phase. Dexamethasone affected glucose dynamics in 3 ways: 1) at 2 h, dexamethasone shortened the ascending branch of the negative phase (P < 0.001) of the test, indicating moderate insulin resistance; 2) at 24 h, dexamethasone impaired glucose clearance by extending the positive phase and eliminating the negative phase while insulin was elevated before the CGIT, indicating a decreased response to insulin; and 3) at 72 h, dexamethasone caused a deeper nadir value (P < 0.001) compared with predexamethasone, indicating an increased response to insulin. It was concluded that dexamethasone decreased the response to insulin as early as 2 h and maximally at 24 h. At 72 h, dexamethasone caused an increased response to insulin, which was unexpected.     

Changes in lymphocyte glucocorticoid and beta-adrenergic receptors in veal calves treated with clenbuterol and steroid hormones for growth-promoting purposes

In order to identify possible peripheral markers of illegal treatments with growth-promoting agents in veal calves, beta-adrenergic receptor (beta-AR) and glucocorticoid receptor (GR) concentrations were measured in lymphocytes of 12 male Friesian crossbred calves (six controls and six treated). The animals received a cocktail of anabolic and re-partitioning agents [17beta-oestradiol: 3 x 10 mg intramuscular (i.m.) doses at 17-day intervals; dexamethasone sodium phosphate: 4 mg/day for 6 days and 5 mg/day for six further days dissolved in milk; and clenbuterol: 20 microg/kg/day dissolved in milk for the last 40 days before slaughter]. Blood samples were collected by venipuncture at different time points and lymphocytes were isolated by density gradient centrifugation. Lymphocyte beta-AR and GR levels were measured by binding assays. Treatment with re-partitioning agents caused a significant down-regulation of lymphocyte beta-ARs 19 days after the beginning of clenbuterol administration and at day 55 (after dexamethasone withdrawal, just before slaughter). This phenomenon was partially reversed at day 50, after dexamethasone administration, at which time a significant decrease in GR concentrations also occurred. For both types of receptors, no significant changes in the dissociation constant values were observed at any time point. Lymphocytes express measurable concentrations of beta-ARs and GRs and the measurement of receptor levels highlights the fluctuation of receptor expression due to the dynamic interaction of the drugs used in combination. Lymphocyte receptor determination could therefore be included in a battery of biological assays to detect illegal treatments with anabolic agents in veal calves in the light of a multivariate approach.     

Binding characteristics of swine erythrocyte insulin receptors

Crossbred gilts (controls; n = 7) had 8.8 +/- 1.1% (mean +/- SEM) maximum binding of [125I]insulin to insulin receptors on erythrocytes. The number of insulin-binding sites per cell was 137 +/- 19, with a binding affinity ranging from 7.4 X 10(7)M-1 to 11.2 X 10(7)M-1 and mean of 8.8 X 10(7)M-1. Pregnant sows (n = 5) had a significant increase (P less than 0.01) in maximum binding due to an increase in number of receptor sites per cell. Lactating sows fed a high-fiber diet (n = 3) and a low-fiber diet (n = 4) did not develop a significant difference in maximum binding of insulin. Sows fed the low-fiber diet had a significantly higher number of binding sites and a significantly lower binding affinity than did sows fed a high-fiber diet. Receptor-binding affinity was lower in the low-fiber diet group than in cycling gilts, whereas data from sows fed the high-fiber diet did not differ from data for cycling gilts. Data from this study indicated that insulin receptors of swine erythrocytes have binding characteristics similar to those in other species. Pregnancy and diet will alter insulin receptor binding in swine.     

Regulation of equine lymphocyte beta-adrenoceptors under the influence of clenbuterol and dexamethasone

In 12 healthy horses, the effects of the beta2-agonist clenbuterol and the glucocorticoid dexamethasone on the lymphocyte beta2-adrenoceptor density and affinity (determined by (-)-[125I]-iodocyanopindolol binding) as well as its responsiveness (assessed by lymphocyte cyclic AMP [cAMP] responses to 10 micromol/l (-)-isoprenaline) were studied. Clenbuterol treatment, 2 x 0.8 microg/kg/day i.v. for 12 days, decreased significantly ICYP binding sites by approximately 30-40%; concomitantly, lymphocyte cAMP response to (-)-isoprenaline was reduced. After withdrawal of clenbuterol, beta2-adrenoceptor density and responsiveness gradually increased, reaching predrug levels after 4 days. The effects of dexamethasone on clenbuterol-induced desensitisation were further investigated. Administration of dexamethasone (1 x 0.1 mg/kg/day, i.v. for 5 days) immediately after clenbuterol withdrawal accelerated beta2-adrenoceptor recovery: only 24 h after administration dexamethasone restored the number of binding sites and cAMP response to (-)-isoprenaline to levels statistically indistinguishable from values before clenbuterol treatment. Three days after dexamethasone administration, lymphocyte beta2-adrenoceptors were further increased about 2-fold the pretreatment values, and this increase declined gradually after dexamethasone withdrawal, reaching baseline values after 4 days. Furthermore, in groups exposed simultaneously to both drugs, dexamethasone completely prevented clenbuterol-induced decrease in lymphocyte beta2-adrenergic receptor density and responsiveness. No significant change was observed in the dissociation constant for ICYP in any of the situations. We conclude that dexamethasone (glucocorticoids) can reverse and prevent Clenbuterol-induced desensitisation (down-regulation) of the lymphocyte beta2-adrenoceptors and therefore, a combined therapy with clenbuterol and dexamethasone may be potentially beneficial in horses suffering from chronic obstructive pulmonary disease (COPD).     

Effects of dexamethasone administration on insulin resistance and components of insulin signaling and glucose metabolism in equine skeletal muscle

ObjecTIVE: To determine the effects of dexamethasone treatment on selected components of insulin signaling and glucose metabolism in skeletal muscle obtained from horses before and after administration of a euglycemic-hyperinsulinemic clamp (EHC). ANIMALS: 6 adult Standardbreds. PROCEDURES: In a balanced crossover study, horses received either dexamethasone (0.08 mg/kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution, IV, for 21 days. A 2-hour EHC was administered for measurement of insulin sensitivity 1 day after treatment. Muscle biopsy specimens obtained before and after the EHC were analyzed for glucose transporter 4, protein kinase B (PKB), glycogen synthase kinase (GSK)-3alpha/beta protein abundance and phosphorylation state (PKB Ser(473) and GSK-3alpha/beta Ser(21/9)), glycogen synthase and hexokinase enzyme activities, and muscle glycogen concentration. RESULTS: Dexamethasone treatment resulted in resting hyperinsulinemia and a significant decrease (70%) in glucose infusion rate during the EHC. In the dexamethasone group, increased hexokinase activity, abrogation of the insulin-stimulated increase in glycogen synthase fractional velocity, and decreased phosphorylation of GSK-3alpha Ser(21) and GSK-3B Ser(9) were detected, but there was no effect of dexamethasone treatment on glucose transporter 4 content and glycogen concentration or on PKB abundance and phosphorylation state. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, 21 days of dexamethasone treatment resulted in substantial insulin resistance and impaired GSK-3 phosphorylation in skeletal muscle, which may have contributed to the decreased glycogen synthase activity seen after insulin stimulation.     

Effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses

OBJECTIVE: To determine effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses. ANIMALS: 6 adult Standardbreds. PROCEDURES: In a balanced crossover study, horses received dexamethasone (0.08 mg/ kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution (control treatment) during a 21-day period. Horses underwent a 3-hour frequently sampled IV glucose tolerance test (FSIGT) 2 days after treatment. Minimal model analysis of glucose and insulin data from FSIGTs were used to estimate insulin sensitivity (Si), glucose effectiveness (Sg), acute insulin response to glucose (AIRg), and disposition index. Proxies for Si (reciprocal of the inverse square of basal insulin concentration [RISQI]) and beta-cell responsiveness (modified insulin-to-glucose ratio [MIRG]) were calculated from basal plasma glucose and serum insulin concentrations. RESULTS: Mean serum insulin concentration was significantly higher in dexamethasone-treated horses than control horses on days 7, 14, and 21. Similarly, mean plasma glucose concentration was higher in dexamethasone-treated horses on days 7, 14, and 21; this value differed significantly on day 14 but not on days 7 or 21. Minimal model analysis of FSIGT data revealed a significant decrease in Si and a significant increase in AIRg after dexamethasone treatment, with no change in Sg or disposition index. Mean RISQI was significantly lower, whereas MIRG was higher, in dexamethasone-treated horses than control horses on days 7, 14, and 21. CONCLUSIONS AND CLINICAL RELEVANCE: The study revealed marked insulin resistance in healthy horses after 21 days of dexamethasone administration. Because insulin resistance has been associated with a predisposition to laminitis, a glucocorticoid-induced decrease in insulin sensitivity may increase risk for development of laminitis in some horses and ponies.     

Increased nuclear type II estradiol receptor concentrations in rat spleen during the course of pregnancy.

Estradiol receptors are classified into type I and type II receptors by their affinity and capacity for estradiol binding. The type II receptors are thought to be significant in the suppression of immune response, such as in the pregnancy-associated immunosuppression. The present study was undertaken to show the presence of type II receptors in rat spleen and to examine the change of receptor distribution after estradiol administration and during pregnancy. Scatchard analysis revealed that the type II receptors were present in rat spleen, and dissociation constants were estimated to be 3.23 x 10(-9) M for cytosol and 4.29 x 10(-9) M for nuclei. The receptors possessed specificity for estradiol and diethylstilbestrol, but not for promegestone, methyltrienolone and dexamethasone. Administration of estradiol to rats resulted in the increase of nuclear receptor concentrations with concomitant decrease of cytosolic concentrations. During pregnancy, the receptor concentrations were increased in the nuclear fraction, but were not significantly changed in the cytosolic fraction. The dissociation constants of the receptors in pregnant rat spleen (4.77 x 10(-9) M for cytosol and 7.20 x 10(-9) M for nuclei) were similar to those in the non-pregnant control, suggesting the quantitative change of the receptors during pregnancy.     

Triglyceride, Insulin, and Cortisol Responses of Ponies to Fasting and Dexamethasone Administration

Ponies were evaluated for their response to feed withholding and exogenous administration of corticosteroids (dexamethasone 0.04 mg/kg intramuscular [IM]) in an attempt to reproduce the hyperlipemia syndrome. Because insulin resistance has been associated with hyperlipemia, all ponies were initially evaluated for insulin response to an oral glucose load and normal dexamethasone suppression of serum cortisol. Four ponies were identified as hyperinsulinemic reflecting insulin resistance. All ponies had suppressed cortisol concentrations following dexamethasone administration. Feed withdrawal resulted in hypertriglyceridemia by 48 hours in all ponies. Very low density lipoprotein-triglyceride (VLDL) fraction was primarily elevated. The administration of dexamethasone failed to increase the degree of triglyceridemia. Although insulin resistance has been proposed as the likely cause of the hypertriglyceridemia in ponies, in this study four of eight ponies were considered to have normal insulin responses and yet still developed hypertriglyceridemia.     

Exercise induced hormonal and metabolic changes in Thoroughbred horses: effects of conditioning and acepromazine

Nine Thoroughbred horses were assessed to determine the normal response of insulin, glucose, cortisol, plasma potassium (K) and erythrocyte K through conditioning and to exercise over 400 and 1,000 m. In addition, adrenaline, noradrenaline, cortisol, plasma K, erythrocyte K and L-lactate concentrations were evaluated in response to maximal exercise with and without the administration of acepromazine. Conditioning caused no obvious trends in plasma K, erythrocyte K, insulin or glucose concentration. Serum cortisol increased (P less than 0.05) from the initial sample at Week 1 to Weeks 4 and 5 (attributed to a response to training), and then decreased. During conditioning, three horses had low erythrocyte K concentrations (less than 89.3 mmol/litre). Further work is needed to define the significance of low erythrocyte K concentrations in the performance horse. In all tests maximal exercise increased plasma K, glucose and cortisol concentrations, whereas insulin and erythrocyte K concentrations decreased. Thirty minutes following exercise, plasma K and erythrocyte K concentrations returned to resting values; whereas glucose and cortisol concentrations continued to increase and the insulin concentration also was increased. The magnitude of the changes varied for pre-conditioned vs post-conditioned exercise tests and the duration of exercise. The administration of acepromazine prior to exercise over 1,000 m failed to alter the circulating noradrenaline and adrenaline concentrations in anticipation of exercise or 2 mins following exercise. Acepromazine administration, however, did cause lower L-lactate concentration 2 mins (P less than 0.03) and 30 mins (P less than or equal to 0.005) following exercise. Also, erythrocyte K showed a delayed return to baseline levels at 30 mins post exercise. Further evaluation of these trends may help explain the beneficial role acepromazine plays in limiting signs of exertional rhabdomyolysis when administered prior to exercise.     

Furosemide-induced electrolyte depletion associated with echinocytosis in horses.

Echinocytes have been incriminated in the pathogenesis of exertional diseases in horses. To evaluate the hypothesis that echinocytes are dehydrated erythrocytes, we decreased blood sodium and potassium concentrations in 4 horses by administering furosemide (1.0 mg/kg of body weight, q 12 h) for 2 days and we monitored CBC, serum and erythrocyte sodium and potassium concentrations, and echinocyte numbers. Serum sodium concentration decreased progressively over the 48 hours of furosemide administration, then returned to near baseline concentration at 168 hours. A statistically significant decrease (P < 0.05) in serum potassium concentration was observed at 24, 48, and 72 hours after initial furosemide administration, and remained less than the baseline value at the end of the study. Mean erythrocyte potassium concentration decreased rapidly and remained low at the end of the study. Minimal changes were observed in erythrocyte sodium concentration during the first 72 hours after furosemide administration, but the value was significantly (P < 0.05) increased at 168 hours. Type-I and type-II echinocyte numbers increased by 4 hours after furosemide administration and persisted throughout the study. Type-III echinocytes were not seen in baseline samples, but numbers increased only modestly after furosemide administration. Administration of epinephrine to well-hydrated horses increased echinocyte numbers only minimally, indicating that splenic contraction was not the likely cause for the furosemide-associated increase. To determine whether the decrease in erythrocyte potassium concentration and increase in sodium concentration was caused by furosemide acting directly on the erythrocyte membrane, we quantified erythrocyte potassium and sodium concentrations before and after incubation with furosemide in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental onion-induced hemolytic anemia in dogs

Within one day following a single oral dose of dehydrated onions, dogs were found to have large numbers of Heinz bodies within erythrocytes. The percentage of erythrocytes that contained Heinz bodies increased slightly to a maximum on day 3 and then declined. The turbidity index increased more gradually with a maximal value on day 4. Erythrocytes with hemoglobin contracted to one side of the cell (eccentrocytes) also appeared after onion feeding. Eccentrocytes are believed to result from a direct injury to the erythrocyte membrane. As with Heinz body-containing cells, the percentages of eccentrocytes present declined as anemia developed. The packed cell volume began to decrease one day after onion administration. A mean decrease of 19 percentage points was reached by day 5. The most anemic dogs had evidence of intravascular hemolysis. Reticulocytosis was first observed five days after onion administration. A slight increase in methemoglobin content was measured four hours after onion administration. No significant changes in erythrocyte reduced glutathione concentration were measured. Transient neutrophilia occurred concomitant with the peak reticulocyte response.     

Exercise Induced Alterations in the Serum Muscle Enzymes, Erythrocyte Potassium and Plasma Constituents Following Feed Withdrawal or Furosemide and Sodium Bicarbonate Administration in the Horse

Six thoroughbreds were used in each of three trials to examine the effect of potassium depletion on exercise-associated muscle damage. Horses were exercised after a control period (Treatment 1), a 72-hour fast (Treatment 2), and furosemide and sodium bicarbonate (Treatment 3). During the preexercise period, feed withdrawal for 72 hours caused decreases in body weight, plasma sodium, chloride, and serum calcium. There were no changes in plasma potassium, erythrocyte potassium, or serum creatine phosphokinase (CK) activity. Furosemide and sodium bicarbonate administration resulted in a decrease in plasma potassium, chloride, serum calcium, and magnesium in the pre-exercise period. Erythrocyte potassium and serum CK activity were unchanged. Body weight initially decreased following furosemide and sodium bicarbonate and then increased upon access to water. In all three treatment groups plasma sodium, potassium, L-lactate, serum calcium, and magnesium were increased immediately following exercise. There was a significant increase (P less than 0.05) in serum CK activity in the furosemide and sodium bicarbonate-treated horses compared to control and withholding feed treatment groups by 30 minutes following exercise. Erythrocyte potassium was decreased immediately following exercise in the furosemide and sodium bicarbonate group but not in the other treatment groups. Potassium depletion may play a role in exercise-induced muscle damage but could not be implicated as the sole cause of the serum CK activity increase in this study.     

Anovulation and plasma hormone concentrations after administration of dexamethasone during the middle of the luteal phase in sows undergoing estrous cycles

The effect of glucocorticoids on early follicular growth in sows undergoing normal estrous cycles was evaluated by administration of dexamethasone during the middle of the luteal phase. Plasma specimens were obtained for measurement of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone, and estradiol-17 beta concentrations. Fifteen sows were used. Control sows (n = 5) were given physiologic saline solution twice daily from day 9 to day 14 of the estrous cycle. Sows of the second group (n = 5) were given dexamethasone (30 micrograms/kg of body weight, IM) similarly, and those of the third group (n = 5) were given dexamethasone plus gonadotropin-releasing hormone (GnRH; 50 micrograms at 6-hour intervals, IV). Plasma specimens, obtained twice daily from day 8 through day 26, indicated that progesterone production and luteal regression were not inhibited by any of the 3 treatment regimens. Although preovulatory plasma estradiol concentration increased in control sows, such was not observed in the sows treated with dexamethasone or dexamethasone plus GnRH (P less than 0.01). Ovulation, with formation of corpora lutea, occurred in gilts given saline solution. Dexamethasone administration resulted in persistence of 19 to 41 follicles/ovary (2 to 4 mm in diameter), and dexamethasone-plus-GnRH treatment resulted in 6 to 18 follicles/ovary (5 to 6 mm in diameter). Plasma was obtained at 15-minute intervals for 12 hours to compare the effect of treatment on hormone concentrations on day 12 of the estrous cycle with the values on day 8.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of colostrum feeding and glucocorticoid administration on insulin-dependent glucose metabolism in neonatal calves

Colostrum feeding and glucocorticoid administration affect glucose metabolism and insulin release in calves. We have tested the hypothesis that dexamethasone as well as colostrum feeding influence insulin-dependent glucose metabolism in neonatal calves using the euglycemic-hyperinsulinemic clamp technique. Newborn calves were fed either colostrum or a milk-based formula (n=14 per group) and in each feeding group, half of the calves were treated with dexamethasone (30 microg/[kg body weight per day]). Preprandial blood samples were taken on days 1, 2, and 4. On day 5, insulin was infused for 3h and plasma glucose concentrations were kept at 5 mmol/L+/-10%. Clamps were combined with [(13)C]-bicarbonate and [6,6-(2)H]-glucose infusions for 5.5h (i.e., from -150 to 180 min, relative to insulin infusion) to determine glucose turnover, glucose appearance rate (Ra), endogenous glucose production (eGP), and gluconeogenesis before and at the end of the clamp. After the clamp liver biopsies were taken to measure mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate carboxylase (PC). Dexamethasone increased plasma glucose, insulin, and glucagon concentrations in the pre-clamp period thus necessitating a reduction in the rate of glucose infusion to maintain euglycemia during the clamp. Glucose turnover and Ra increased during the clamp and were lower at the end of the clamp in dexamethasone-treated calves. Dexamethasone treatment did not affect basal gluconeogenesis or eGP. At the end of the clamp, dexamethasone reduced eGP and PC mRNA levels, whereas mitochondrial PEPCK mRNA levels increased. In conclusion, insulin increased glucose turnover and dexamethasone impaired insulin-dependent glucose metabolism, and this was independent of different feeding.     

Effect of dietary fructans and dexamethasone administration on the insulin response of ponies predisposed to laminitis

OBJECTIVE: To determine whether pasture, and specifically the addition of fructan carbohydrate to the diet, induces exaggerated changes in serum insulin concentration in laminitispredisposed (LP) ponies, compared with ponies with no history of the condition, and also to determine insulin responses to the dexamethasone suppression test. DESIGN: Prospective study. ANIMALS: 10 LP and 11 control adult nonobese mixed-breed ponies. PROCEDURES: Insulin-modified IV glucose tolerance tests were performed (5 ponies/group). In diet studies, ponies were kept on pasture and then changed to a hay diet (10 ponies/group). Second, ponies were maintained on a basal hay diet (4 weeks) before being fed a hay diet supplemented with inulin (3 g/kg/d [1.4 g/lb/d]). Serum insulin and plasma glucose concentrations were analyzed before and after dietary changes. Serum cortisol and insulin concentrations were also measured in a standard dexamethasone suppression test. RESULTS: The LP ponies were insulin resistant (median insulin sensitivity of 0.27 x 10(4) L min(-1) mU(-1) in LP ponies, compared with 0.64 x 10(4) L min(-1) mU(-1) in control ponies). Median insulin concentration in LP ponies was significantly greater than that in control ponies at pasture, decreased in response to feeding hay, and was markedly increased (5.5-fold) following the feeding of inulin with hay. The LP ponies had a greater increase in serum insulin concentration at 19 hours after dexamethasone administration (median, 222.9 mU/L), compared with control ponies (45.6 mU/L). CONCLUSIONS AND CLINICAL RELEVANCE: Nonobese ponies predisposed to develop laminitis had compensated insulin resistance, and this phenotype was revealed by feeding plant fructan carbohydrate or by dexamethasone administration.     

Efficacy of protamine zinc insulin for treatment of diabetes mellitus in cats

OBJECTIVE: To evaluate effects of protamine zinc insulin (PZI) on control of glycemia in cats with newly diagnosed diabetes mellitus or poorly controlled diabetes. DESIGN: Clinical trial. ANIMALS: 67 diabetic cats. PROCEDURE: 34 cats with newly diagnosed diabetes and 33 cats with poorly controlled diabetes were treated with PZI twice daily for 45 days. Control of glycemia was assessed on days 7, 14, 30, and 45 by evaluation of clinical response, change in body weight, serum fructosamine concentration, blood glucose concentration measured 1, 3, 5, 7, and 9 hours after administration of PZI, lowest blood glucose concentration, and mean blood glucose concentration during the 9-hour period after administration. Adjustments in dosage of PZI were made as needed to attain control of glycemia. RESULTS: For all cats, a significant increase in mean dosage of PZI and significant decreases in 9-hour mean blood glucose concentration, lowest mean blood glucose concentration, and mean serum fructosamine concentration were detected. For cats with poorly controlled diabetes, 9-hour mean blood glucose concentration and mean serum fructosamine concentration were significantly decreased on day 45, compared with day 0. Ninety percent of owners reported improvement or resolution of clinical signs by day 45. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that PZI was effective for control of glycemia in cats with newly diagnosed or poorly controlled diabetes and may be used as an initial treatment or as an alternative treatment in cats that do not respond to treatment with other types of insulin.     

Purification and characterization of a feline hepatic insulin receptor

OBJECTIVE: To elucidate the functional characteristics of a highly purified soluble liver insulin receptor in cats. SAMPLE POPULATION: Frozen livers from domestic cats were obtained commercially. PROCEDURES: The feline hepatic insulin receptor was purified from Triton X-100 solubilized plasma membranes by the use of several chromatography matrices, including affinity chromatography on an insulin-Sepharose matrix. RESULTS: The receptor, although not homogeneous, was purified 3,000-fold. Two silver-stained protein bands were identified following sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with molecular weight of 134,000 and 97,000, which are similar to insulin receptors isolated from other animals. This isolated receptor had steady-state insulin binding by 40 minutes at 24 C. Optimal insulin binding occurred at pH 7.8 and with 150 mM NaCl. Under these conditions, a curvilinear Scatchard plot was obtained with the isolated receptor. Using a 2 binding-site model, the feline insulin receptor had a high-affinity low-capacity site with a dissociation constant (KD; nM) of 3 and a low-affinity high-capacity site with a K(D) of 1,180. The receptor also had tyrosine kinase activity toward an exogenous substrate that was stimulated by insulin and protamine. CONCLUSIONS AND CLINICAL RELEVANCE: Many of the reported characteristics of the liver insulin receptor in cats are similar to those for the receptor isolated from other animals and tissues, although some differences exist. These similarities suggest that characterization of the feline insulin receptor is important to understanding insulin resistance in cats with diabetes as well as in humans with diabetes.     

Comparison of serum dexamethasone concentrations in cats after oral or transdermal administration using pluronic lecithin organogel (PLO): a pilot study

The objective of this study was to measure and compare the serum concentrations of dexamethasone after oral and transdermal administration using pluronic lecithin organogel in six healthy cats. The study was designed as a crossover, in which the cats were randomly assigned to two groups. The cats received a single dose (0.05 mg kg(-1)) of dexamethasone either orally or transdermally on the inner pinna. Blood samples were taken at 0, 5, 15, 30, 60, 90 and 120 min, and 3, 4, 6, 8, 12 and 24, 48 and 72 h post dexamethasone administration. A mean peak serum concentration of 30.1 ng mL(-1) was detected 15 min after oral administration. Serum concentrations were below detection limits by 24 h. In contrast, there was no significant increase in serum concentrations of dexamethasone after transdermal administration. In cats, transdermal administration of a single dose of dexamethasone did not result in significant serum concentrations compared to oral administration.