Secretion In Dogs Research Articles

Preliminary comparative serological evaluation of Histamine H2 receptors in dogs with an acute onset of vomiting treated with Ranitidine and healthy dogs

Despite the lack of evidence of the ability to suppress gastric acid secretion in dogs, ranitidine (RT) is often used to control clinical signs in dogs with acute vomiting even if the way it happens it is still largely unknown. The aim of this study was thus to evaluate the therapeutic effect of ranitidine on H2 receptors in dogs with acute vomiting. To investigate the RT activity a preliminary study was performed in dogs which underwent gastroscopy analyses, demonstrating that the level of H2R observed in the serum and gastric wall tissue was the same [1.473(1.30; 1.79) ng/ml and 1.498 (1.33; 1.85) ng/ml, respectively]. After that H2R levels in the serum of 22 healthy dogs (Group 1) and in a group of 22 dogs with acute vomiting (Group 2) were compared both before (T0), after 7–10 days (T1) of 2 mg/kg twice a day ranitidine administration and after 11 days since the drug was discontinued (T2). Significant differences (p<0.001) were detected between the level of circulating H2R among Group 1: 0.41 ng/ml (0.28;0.54) and Group 2: 2.27 ng/ml (2.11;2.49) at T0. In Group 2, no difference in the level of H2R was detected in samples collected at T0 compared to those at T1 [T1: 2.32 ng/ml (2.14; 2.49)] and T2 [T2: 2.30 ng/ml (1.99;2.69)]. In Group 2 all patients but one displayed remission of symptoms attributable to inflammatory gastropathy at the first withdrawal (T1: 7–10 days), while at the second withdrawal (T2: after 21 days), remission was detected in all dogs. Our preliminary hypothesis is that the clinical efficacy of ranitidine is related to the greater expression of H2 receptors in patients with acute vomiting. This increased expression may be due to continuous pathological stimulus at the gastric level. Further studies with a wider population are needed to better investigate the activity of RT in dogs with acute onset of vomiting.

Tegoprazan, a Novel Potassium-Competitive Acid Blocker to Control Gastric Acid Secretion and Motility.

Tegoprazan [(S)-4-((5,7-difluorochroman-4-yl)oxy)-N,N,2-trimethyl-1H-benzo[d]imidazole-6-carboxamide], a potassium-competitive acid blocker (P-CAB), is a novel potent and highly selective inhibitor of gastric H+/K+-ATPase. Tegoprazan inhibited porcine, canine, and human H+/K+-ATPases in vitro with IC50 values ranging from 0.29 to 0.52 μM, while that for canine kidney Na+/K+-ATPase was more than 100 μM. A kinetic analysis revealed that tegoprazan inhibited H+/K+-ATPase in a potassium-competitive manner and the binding was reversible. Oral single administrations of tegoprazan ranging from 0.3 to 30 mg/kg in dogs were well absorbed into the blood stream and distributed in gastric tissue/fluid higher than in plasma. Tegoprazan potently inhibited histamine-induced gastric acid secretion in dogs, and a complete inhibition was observed at 1.0 mg/kg starting from 1 hour after administration. Moreover, an oral administration of tegoprazan at 1 and 3 mg/kg reversed the pentagastrin-induced acidified gastric pH to the neutral range. Interestingly, 3 mg/kg tegoprazan immediately evoked a gastric phase III contraction of the migrating motor complex in pentagastrin-treated dogs and similar effects was observed with the other P-CAB, vonoprazan. Tegoprazan is the novel P-CAB that may provide a new option for the therapy of gastric acid-related and motility-impaired diseases.

Genome Sequence of Canine Polyomavirus in Respiratory Secretions of Dogs with Pneumonia of Unknown Etiology.

ABSTRACTWe report here the first canine polyomavirus genome, identified by metagenomics in respiratory secretions of two dogs with severe pneumonia, which tested negative for all canine respiratory pathogens except Mycoplasma cynos. The isolate, Canis familiaris polyomavirus 1 (DogPyV-1), is a beta polyomavirus whose closest known LT antigen relatives are primate polyomaviruses.

Decreased Insulin Secretion in Dogs with Chronic Mitral Valve Insufficiency

Glucose metabolism abnormalities secondary to heart failure, including insulin resistance (IR) and impaired fasting glucose, have been gradually recognized as important prognostic factors in disease progression. However, to date, no study has investigated glucose abnormalities in dogs with chronic mitral valve insufficiency (CMVD). Thus, we hypothesized that glucose metabolism abnormalities due to heart failure may develop in dogs with CMVD. A prospective study was performed on 113 client-owned dogs with variable CMVD severities. Serum insulin, glucagon, fructosamine, and glucose concentrations were measured, and insulin resistance was determined using the homeostatic model assessment (HOMA) score. The serum insulin concentration had a significant inverse association with the heart failure severity. However, there was no significant association between the heart failure severity and fructosamine, HOMA score, and fasting blood glucose. Insulin, fructosamine, and HOMA had a significant positive association with body condition scores (BCS), whereas glucose had no association. This study found that insulin secretion in dogs with naturally occurring heart failure due to CMVD might be compromised as the disease worsens.

Effect of rhythmic pressure waves on balancing airway basic mucus secretion in dogs

To investigate the effect of different pressure on mucin (MUC) secretion in dog airway mucus layer and explore the participation mechanisms. Totally 24 healthy dogs were randomly divided into 4 groups (n=6) after double-lumen endobronchial tube intubation. In group A the dogs were ventilated bilaterally with normal breathing frequency and pressure; In group B: one side of the dog lung did not ventilate, while the other side was excessively ventilated. In group C: the tension-sensitive cation channel (TRPV) 4 blocker Ruthenium Red (RR) was injected in advance, and ventilated as in group A. In group D: TRPV4 blocker RR was injected firstly, and then ventilated as in group B. After 12 h ventilation, we collected bronchoalveolar lavage fluid (BALF), tested MUC (2, 5AC, 5B) protein content by ELISA, and detected the transcription of MUC (2, 5AC, 5B) mRNA of bronchial lung tissue by RTPCR. Compared with the normal ventilation (A2) group, the protein level of MUC of excessive ventilation (B2) group was significantly higher, mainly MUC5AC (P<0.05); compared with the normal ventilation (A1) group, the protein level of MUC of no ventilation (B1) group was significantly decreased (P<0.05). After pretreatment with RR, the MUC protein level of group C1, C2 were significantly lower than that of group A1, A2 (P<0.05); the MUC protein level of group B2were significantly lower than that of group D2 (P<0.05). The MUC (2, 5AC and 5B) mRNA level was higher in excessive ventilation group (B2) than in normal ventilation group (A2). After pretreatment with RR, in comparison with group A1, A2, the MUC (2, 5AC and 5B) mRNA level of group C1, C2 declined; in comparison with group B2, the MUC (2, 5AC and 5B) mRNA level of group D2 declined. Rhythmic pressure waves may regulate and balance basic airway mucin secretion through activating the TRPV4 channel in dogs.

Clinical and Immunomodulatory Effects of Toceranib Combined with Low‐Dose Cyclophosphamide in Dogs with Cancer

Tyrosine kinase inhibitors (TKIs) and metronomic dosing of cyclophosphamide (CYC) can improve tumor control by suppression of regulatory T cells (Treg) and restoration of T cell-mediated immune responses in mice and humans. The immunomodulatory effects of the TKI toceranib, as a single agent or in combination with metronomic CYC, have not been previously investigated in dogs. The primary objectives of this study were to determine the effects of toceranib and metronomic CYC treatment on lymphocyte subsets including Treg and on interferon-gamma (IFN-γ) secretion in dogs with cancer. We hypothesized that toceranib would selectively decrease Treg numbers and increase IFN-γ production and that addition of CYC would further enhance these effects. Fifteen client-owned dogs with advanced tumors were entered into a prospective clinical trial. Dogs received toceranib at 2.75 mg/kg once every other day. After 2 weeks, oral CYC was added at 15 mg/m(2) daily. Numbers of Treg and lymphocyte subsets were measured in blood by flow cytometry during the 8-week study period. Serum concentrations of IFN-γ were measured by ELISA. Administration of toceranib significantly decreased the number and percentage of Treg in the peripheral blood of dogs with cancer. Dogs receiving toceranib and CYC demonstrated a significant increase in serum concentrations of IFN-γ, which was inversely correlated with Treg numbers after 6 weeks of combination treatment. In addition to antitumor effects, these data support further investigations into the immunomodulatory effects of toceranib, administered alone or in combination with CYC in dogs with cancer.

Basal measures of insulin sensitivity and insulin secretion and simplified glucose tolerance tests in dogs

There is need for simple, inexpensive measures of glucose tolerance, insulin sensitivity, and insulin secretion in dogs. The aim of this study was to estimate the closeness of correlation between fasting and dynamic measures of insulin sensitivity and insulin secretion, the precision of fasting measures, and the agreement between results of standard and simplified glucose tolerance tests in dogs. A retrospective descriptive study using 6 naturally occurring obese and 6 lean dogs was conducted. Data from frequently sampled intravenous glucose tolerance tests (FSIGTTs) in 6 obese and 6 lean client-owned dogs were used to calculate HOMA, QUICKI, fasting glucose and insulin concentrations. Fasting measures of insulin sensitivity and secretion were compared with MINMOD analysis of FSIGTTs using Pearson correlation coefficients, and they were evaluated for precision by the discriminant ratio. Simplified sampling protocols were compared with standard FSIGTTs using Lin's concordance correlation coefficients, limits of agreement, and Pearson correlation coefficients. All fasting measures except fasting plasma glucose concentration were moderately correlated with MINMOD-estimated insulin sensitivity (| r| = 0.62–0.80; P < 0.03), and those that combined fasting insulin and glucose were moderately closely correlated with MINMOD-estimated insulin secretion ( r = 0.60–0.79; P < 0.04). HOMA calculated using the nonlinear formulae had the closest estimated correlation ( r = 0.77 and 0.74) and the best discrimination for insulin sensitivity and insulin secretion (discriminant ratio 4.4 and 3.4, respectively). Simplified sampling protocols with half as many samples collected over 3 h had close agreement with the full sampling protocol. Fasting measures and simplified intravenous glucose tolerance tests reflect insulin sensitivity and insulin secretion derived from frequently sampled glucose tolerance tests with MINMOD analysis in dogs.

The long-lasting effect of TU-199, a novel H+, K(+)-ATPase inhibitor, on gastric acid secretion in dogs.

We have used Heidenhain-pouch dogs to investigate the effects of (+/-)-5-methoxy-2-{[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulph inyl}-1H-imidazo[4,5-b]pyridine (TU-199), an imidazopyridine derivative, on gastric acid secretion stimulated by histamine, carbachol and tetragastrin. We have also investigated the duration of the antisecretory effect of TU-199 using a measurement of intragastric pH for 24 h in gastric fistula dogs whose gastric acid secretion was stimulated by histamine. Single oral administration of TU-199 (0.1, 0.2 and 0.4mgkg(-1)) dose-dependently suppressed gastric acid secretion stimulated by histamine infusion. Oral treatment with TU-199 (0.2, 0.4 and 0.8 mg kg(-1)) also dose-dependently inhibited acid secretion induced by carbachol and tetragastrin. The inhibitory effect of TU-199 on stimulated gastric acid secretion was more potent than that of omeprazole, a well-known H+,K(+)-ATPase inhibitor in dogs. Repeated oral treatment with TU-199 at a dose of 0.2 mg kg(-1) once a day for seven days markedly suppressed histamine-stimulated gastric acid secretion in dogs. This inhibitory effect of TU-199 reached a maximum level after three or four doses and was more pronounced than that of omeprazole or lansoprazole. In gastric fistula dogs, the duration of intragastric pH-elevation by administration of TU-199 (0.3 mg kg(-1)) was much longer than that of omeprazole (0.6mgkg(-1)) or lansoprazole (0.9mgkg(-1)). The IC50 values (doses resulting in 50% inhibition) of TU-199, omeprazole and lansoprazole with regard to H+,K(+)-ATPase activity in dog gastric mucosal microsomes were 8.6, 8.8 and 9.9 microM, respectively. These results indicate that TU-199 inhibits gastric acid secretion via suppression of a H+,K(+)-ATPase activity. Our findings also suggest that TU-199 might have potent and long-lasting effects on gastric acid secretion.

A comparative study by age and gender of the pituitary adenoma and ACTH and α-MSH secretion in dogs with pituitary-dependent hyperadrenocorticism

Pituitary-dependent hyperadrenocorticism (PDH) is frequent in dogs. Little is known about its presentation in different age groups and its characteristics. Dividing the population under study ( n = 107) into three age groups we observed that 11.2% were young, 51.4% adults and 37.4% aged. Using magnetic resonance, pituitary tumours were intra-sellar (IS) in 30.8% and extra-sellar (ES) in 62.6% and the pars intermedia (PI) was affected in 6.5%. ES are predominant in females and IS in males ( p < 0.0001). In the adult-aged population, the ES and PI are predominant, while in the young, the IS predominate ( p < 0.0001). ACTH concentration was greater in the ES vs. IS ( p < 0.05). α-MSH did not present significant differences according to tumour size, showing a negative correlation ( r = −0.47; p < 0.01) vs. ACTH. Differences in adenoma size according to gender and their age-related frequency of apparition could be because of different origins of the corticotrophinoma.

Effect of Free Dietary Glutamate on Gastric Secretion in Dogs

The amino acid, L-glutamate, which is abundant in many foodstuffs, is a potent stimulator of gastric vagal afferents. The aim of the study was to evaluate a role of dietary glutamate in neuroendocrine control of gastric secretion of acid, pepsinogen, and fluid. In mongrel dogs with small gastric pouches surgically prepared according to Pavlov (vagally innervated) or Heidenhain (vagally decentralized), secretion in a pouch was induced by infusion into the main stomach of an amino acid-rich diet lacking glutamate (Elental) or the same diet supplemented with monosodium glutamate (MSG). Having no effect alone, MSG (100 mM) potentiated secretion induced by Elental both in Pavlov and Heidenhain models. In the Pavlov pouch, the effect of MSG was markedly reduced after i.v. injection of granisetron, an antagonist of 5-HT(3) receptors. In the Heidenhain model, MSG enhanced the stimulatory effect of pentagastrin (1 microg/kg, s.c.). In conclusion, dietary glutamate at doses not exceeding its common concentrations in foods substantially potentiates gastric phase secretion induced by stimulation of gastric mucosa with an amino acid-rich diet or by administration of pentagastrin. The effect of glutamate is partially mediated via serotonin secretion and stimulation of 5-HT(3) receptors.

Intracerebroventricular infusion of neuropeptide Y modulates VIP secretion in the fasting conscious dog

Intracerebroventricular (icv) injection of neuropeptide Y (NPY), which is a widely-distributed neurotransmitter, into the paraventricular nuclear area has been shown previously to increase secretion of insulin and glucagon from the pancreatic islets. Vasoactive intestinal polypeptide (VIP) is a 28-amino-acid peptide that is associated with the mobilisation of energy during situations of energy depletion, such as fasting and exercise. VIP has also been reported to alter insulin and glucagon levels in a glucose-dependent manner. The aim of this study was to determine whether icv infusion of NPY affected VIP secretion in dogs. Intracerebroventricular injections (0.5 ml) were administered through a stereotactic apparatus to six healthy dogs. This prototype epicranial apparatus was positioned surgically to allow the easy and exact localisation of the third ventricle for infusion or sampling. Doses of 5, 10, and 25 microg NPY, dissolved in artificial cerebrospinal fluid (aCSF), were infused for a total of 30 min using a Harvard infusion pump. For control experiments, aCSF alone was injected. Blood samples were taken 15 min before icv injection (basal), immediately after injection, and at 5, 10, 15, 30, 45, 60, 90, and 120 min after, to determine the levels of glucose, insulin, glucagon, and VIP. Intracerebroventricular infusion of NPY resulted in a short-term increase in VIP secretion, followed by a more gradual and lengthier decrease in VIP levels. The secretion of insulin and glucagon increased significantly with all three doses of NPY. Intracerebroventricular infusion of NPY increased secretion of insulin and glucagon from the pancreas. The rapid change in the levels of VIP suggested the possibility of neural regulation by NPY.

Novel Nucleotide Human Immunodeficiency Virus Reverse Transcriptase Inhibitor GS-9148 with a Low Nephrotoxic Potential: Characterization of Renal Transport and Accumulation

Accumulation of antiviral nucleotides in renal proximal tubules is controlled by their basolateral uptake via the human renal organic anion transporters type 1 (hOAT1) and 3 (hOAT3) and apical efflux via the multidrug resistance protein 4 (MRP4). GS-9148 is a novel ribose-modified nucleotide human immunodeficiency virus (HIV) reverse transcriptase inhibitor, and its oral prodrug GS-9131 is currently being evaluated in the clinic as an anti-HIV agent. To assess the potential of GS-9148 for nephrotoxicity, its mechanism of renal transport, cytotoxicity, and renal accumulation were explored in vitro and in vivo. In comparison with the acyclic nucleotides cidofovir, adefovir, and tenofovir, GS-9148 showed 60- to 100-fold lower efficiency of transport (V(max)/K(m)) by hOAT1 and was 20- to 300-fold less cytotoxic in cells overexpressing hOAT1, indicating its lower hOAT1-mediated intracellular accumulation and reduced intrinsic cytotoxicity. GS-9148 was also relatively inefficiently transported by hOAT3. Similar to acyclic nucleotides, GS-9148 was a substrate for MRP4 as evidenced by its reduced intracellular retention in cells overexpressing the efflux pump. Consistent with these molecular observations, GS-9148 was inefficiently taken up by fresh human renal cortex tissue in vitro and showed a limited accumulation in kidneys in vivo following oral administration of [(14)C]GS-9131 to dogs. Compared to acyclic nucleotide analogs, GS-9148 was also found to have lower net active tubular secretion in dogs. Collectively, these results suggest that GS-9148 exhibits a low potential for renal accumulation and nephrotoxicity.

Circadian variations in salivary chromogranin a concentrations during a 24-hour period in dogs

The purpose of this study was to determine if salivary chromogranin a secretion in dogs exhibits a circadian rhythm. Saliva sampling was performed during three different sessions occurring in three nonconsecutive 24-h periods. Sixteen healthy adult beagle dogs (8 males and 8 females) were moved to a sampling room and housed individually in cages. Saliva samples were obtained every 4 h from 12:00 p.m. to 12:00 p.m. the following day. In the interest of habituation, saliva was obtained hourly from each dog 3 h before the experiment was started. Salivary chromogranin A concentrations were measured using an enzyme-linked immunosorbent assay. No circadian rhythm was detected for salivary chromogranin A secretion, and no differences in salivary chromogranin A concentrations measured every 4 h were demonstrated during the 24-h cycle in dogs.

Biology of Incretins: GLP-1 and GIP

This review focuses on the mechanisms regulating the synthesis, secretion, biological actions, and therapeutic relevance of the incretin peptides glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). The published literature was reviewed, with emphasis on recent advances in our understanding of the biology of GIP and GLP-1. GIP and GLP-1 are both secreted within minutes of nutrient ingestion and facilitate the rapid disposal of ingested nutrients. Both peptides share common actions on islet beta-cells acting through structurally distinct yet related receptors. Incretin-receptor activation leads to glucose-dependent insulin secretion, induction of beta-cell proliferation, and enhanced resistance to apoptosis. GIP also promotes energy storage via direct actions on adipose tissue, and enhances bone formation via stimulation of osteoblast proliferation and inhibition of apoptosis. In contrast, GLP-1 exerts glucoregulatory actions via slowing of gastric emptying and glucose-dependent inhibition of glucagon secretion. GLP-1 also promotes satiety and sustained GLP-1-receptor activation is associated with weight loss in both preclinical and clinical studies. The rapid degradation of both GIP and GLP-1 by the enzyme dipeptidyl peptidase-4 has led to the development of degradation-resistant GLP-1-receptor agonists and dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes. These agents decrease hemoglobin A1c (HbA1c) safely without weight gain in subjects with type 2 diabetes. GLP-1 and GIP integrate nutrient-derived signals to control food intake, energy absorption, and assimilation. Recently approved therapeutic agents based on potentiation of incretin action provide new physiologically based approaches for the treatment of type 2 diabetes.

The effects of 10% hypertonic saline, 0.9% saline and hydroxy ethyl starch infusions on hydro-electrolyte status and adrenal function in healthy conscious dogs

The purpose of this study was to investigate the influence of different saline and colloid solutions on adrenal steroid secretion in dogs. Six healthy male Beagles underwent three infusion cycles: 10 min infusion of 30 ml/kg of NaCl 0.9%, 5 ml/kg of hydroxy ethyl starch, or 5 ml/kg of NaCl 10%. Plasma osmolality, hematocrit, total solids, cortisol and aldosterone levels were measured at 0, 5, 15, 30, 60, 120, 180 and 240 min after beginning infusion. Plasma ACTH levels were measured at 0, 15 and 240 min. An identical timing of sampling was applied during a control session omitting the fluid infusion. Osmolality, sodium, chloride and cortisol levels were found to be significantly higher with hypertonic saline solute compared to control. All fluid infusions lead to lowered plasma potassium, hematocrit, total solids and aldosterone values. ACTH concentrations did not show significant changes with any of the infusion cycles. The increase in cortisol levels suggests that hypertonic saline infusion could be interesting in critical care resuscitation, particularly in patients who are suffering from relative adrenal insufficiency.

Thyrotropin-releasing hormone-induced growth hormone secretion in dogs with primary hypothyroidism

Primary hypothyroidism in dogs is associated with increased release of growth hormone (GH). In search for an explanation we investigated the effect of intravenous administration of thyrotropin-releasing hormone (TRH, 10 μg/kg body weight) on GH release in 10 dogs with primary hypothyroidism and 6 healthy control dogs. The hypothyroid dogs had a medical history and physical changes compatible with hypothyroidism and were included in the study on the basis of the following criteria: plasma thyroxine concentration <2 nmol/l and plasma thyrotropin (TSH) concentration >1 μg/l. In addition, 99mTcO 4 − uptake during thyroid scintigraphy was low or absent. TRH administration caused plasma TSH concentrations to rise significantly in the control dogs, but not in the hypothyroid dogs. In the dogs with primary hypothyroidism, the mean basal plasma GH concentration was relatively high (2.3 ± 0.5 μg/l) and increased significantly ( P = 0.001) 10 and 20 min after injection of TRH (to 11.9 ± 3.5 and 9.8 ± 2.7 μg/l, respectively). In the control dogs, the mean basal plasma GH concentration was 1.3 ± 0.1 μg/l and did not increase significantly after TRH administration. We conclude that, in contrast to healthy control dogs, primary hypothyroid dogs respond to TRH administration with a significant increase in the plasma GH concentration, possibly as a result of transdifferentiation of somatotropic pituitary cells to thyrosomatotropes.

Immunohistolocalization and Gene Expression of the Secretory Carbonic Anhydrase Isozymes (CA‐VI) in Canine Oral Mucosa, Salivary Glands and Oesophagus

The immunohistolocalization of secretory carbonic anhydrase isoenzymes (CA-VI) in canine salivary glands, parotid, submandibular, sublingual and zygomatic glands, oral and oesophageal mucosa was studied using a specific antiserum against a canine CA-VI. In addition, the gene expression of CA-VI from the same tissue was studied using a real-time reverse-transcriptase polymerase chain reaction. In all salivary glands and oesophageal gland, immunostaining intensely localized CA-VI antiserum throughout the cytoplasm of serous acinar cells, including serous demilune and ductal epithelial cells. In contrast, no immunoreaction localized CA-VI in the mucous acinar cells of the gland. CA-VI gene transcripts were also detected in the same areas. The physiological significance of secretory CA-VI in the oral and oesophageal cavity is thought to play a highly specialized role in the maintenance of bicarbonate level in saliva and to protect mucosa from acid injury. It is shown that the major sites of the CA-VI secretion in dogs were in serous (demilune) secretory cells in all four major salivary glands and oesophageal glands in particular.

Pituitary and testicular endocrine responses to exogenous gonadotrophin-releasing hormone (GnRH) and luteinising hormone in male dogs treated with GnRH agonist implants

The present study tested whether exogenous gonadotrophin-releasing hormone (GnRH) and luteinising hormone (LH) can stimulate LH and testosterone secretion in dogs chronically treated with a GnRH superagonist. Twenty male adult dogs were assigned to a completely randomised design comprising five groups of four animals. Each dog in the control group received a blank implant (placebo) and each dog in the other four groups received a 6-mg implant containing a slow-release formulation of deslorelin (d-Trp6-Pro9-des-Gly10-LH-releasing hormone ethylamide). The same four control dogs were used for all hormonal challenges, whereas a different deslorelin-implanted group was used for each challenge. Native GnRH (5 microg kg(-1) bodyweight, i.v.) was injected on Days 15, 25, 40 and 100 after implantation, whereas bovine LH (0.5 microg kg(-1) bodyweight, i.v.) was injected on Days 16, 26, 41 and 101. On all occasions after Day 25-26 postimplantation, exogenous GnRH and LH elicited higher plasma concentrations of LH and testosterone in control than deslorelin-treated animals (P < 0.05). It was concluded that, in male dogs, implantation of a GnRH superagonist desensitised the pituitary gonadotrophs to GnRH and also led to a desensitisation of the Leydig cells to LH. This explains, at least in part, the profound reduction in the production of androgen and spermatozoa in deslorelin-treated male dogs.

Inhalation of Human Insulin Is Associated with Improved Insulin Action Compared with Subcutaneous Injection and Endogenous Secretion in Dogs

This study compared the effects of endogenous (portal) insulin secretion versus peripheral insulin administration with subcutaneous or inhaled human insulin [INH; Exubera, insulin human (rDNA origin) inhalation powder] on glucose disposal in fasted dogs. In the control group, glucose was infused into the portal vein (Endo; n = 6). In two other groups, glucose was infused portally, whereas insulin was administered peripherally by inhalation (n = 13) or s.c. injection (n = 6) with somatostatin and basal glucagon. In the Endo group, over the first 3 h, the arterial insulin concentration was twice that of the peripheral groups, whereas hepatic sinusoidal insulin levels were half as much. Although net hepatic glucose uptake was greatest in the Endo group, the peripheral groups demonstrated larger increases in nonhepatic glucose uptake so that total glucose disposal was greater in the latter groups. Compared with s.c. insulin action, glucose excursions were smaller and shorter, and insulin action was at least twice as great after INH. Thus, at the glucose dose and insulin levels chosen, peripheral insulin delivery was associated with greater whole-body glucose disposal than endogenous (portal) insulin secretion. INH administration resulted in increased insulin sensitivity in nonhepatic but not in hepatic tissues compared with s.c. delivery.

Hormonal disturbances associated with obesity in dogs

Obesity is associated with multiple endocrine alterations and changes in the concentration of circulating hormones. However, few studies have explored such alterations in dogs with naturally acquired excess weight. In the present study, we investigated the effect of naturally acquired obesity on cortisol, insulin-like growth factor (IGF)-1 and prolactin secretion in dogs. Thirty-one overweight dogs were enrolled in the trial. Blood samples were collected before and after adrenocorticotrophic hormone (ACTH) injection. Free thyroxine (fT4), cortisol, thyroid-stimulating hormone (TSH), IGF-1, prolactin and fructosamine were assayed. Body weight excess increased significantly with age and neutered dogs were more obese than entire ones. The ACTH stimulation test was within the normal range for 26 of 31 dogs. Prolactinaemia was increased in seven dogs and IGF-1 in six dogs. Twenty dogs had a fructosamine concentration >340 microm. Interestingly, 18 of 31 dogs showed disturbances of thyroid function based on high TSH and/or low fT4 baseline concentration, with 11 dogs showing both. According to these parameters only six of 31 dogs were free of hormonal disturbances. These results revealed the high incidence of such disturbances, especially thyroid dysfunction, in obese, but otherwise apparently healthy dogs. They demonstrate the importance of examining endocrine function during the initial evaluation of obese dogs to avoid failure of any nutritional treatment.