Circulating concentrations of glucagon-like peptide 1, glucose-dependent insulinotropic peptide, peptide YY, and insulin in client-owned lean, overweight, and diabetic cats.

Our objectives were to measure plasma concentrations of glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY (PYY) in client-owned newly diagnosed diabetic cats and nondiabetic lean or overweight cats and to determine whether circulating concentrations of these hormones differed between study groups and if they increased postprandially as seen in other species. A total of 31 cats were recruited and placed into 1 of 3 study groups: lean (body condition score 4-5 on a scale of 1-9; n = 10), overweight (body condition score 6-8; n = 11), or diabetic (n = 10). Diabetics were newly diagnosed and had not had prior insulin therapy. Preprandial (fasting) and postprandial (60 min after meal) plasma hormone and glucose concentrations were measured at baseline and 2 and 4 wk. All cats were exclusively fed a commercially available high-protein and low-carbohydrate diet commonly prescribed to feline diabetic patients for 2 wk before the 2-wk assessment and continued through the 4-wk assessment. Results showed that plasma concentrations of GLP-1, GIP, PYY, and insulin increased in general after a meal in all study groups. Plasma PYY concentrations did not differ (P > 0.10) between study groups. Diabetics had greater plasma concentrations of GLP-1 and GIP compared with the other study groups at baseline (P < 0.05), and greater preprandial and postprandial GLP-1 concentrations than lean cats at 2 and 4 wk (P < 0.05). Preprandial plasma GIP concentrations were greater in diabetics than obese and lean (P < 0.05) cats at week 4. Postprandial plasma GIP concentrations in diabetics were greater than lean (P < 0.05) at week 2 and obese and lean cats (P < 0.05) at week 4. Together, our findings suggest that diabetic status is an important determinant of circulating concentrations of GLP-1 and GIP, but not PYY, in cats. The role of GLP-1, GIP, and PYY in the pathophysiology of feline obesity and diabetes remains to be determined.

Clinical phenotype of X-linked myotubular myopathy in Labrador Retriever puppies.

BACKGROUND: Seven male Labrador Retriever puppies from 3 different litters, born to clinically normal dams and sires, were evaluated for progressive weakness and muscle atrophy. Muscle biopsies identified a congenital myopathy with pathologic features consistent with myotubular myopathy. Further investigations identified a pathogenic mutation in the myotubularin gene, confirming that these puppies had X-linked myotubular myopathy (XLMTM). OBJECTIVE: To review the clinical phenotype, electrodiagnostic and laboratory features of XLMTM in this cohort of Labrador Retrievers. RESULTS: Male puppies with XLMTM were small and thin compared with their normal littermates. Generalized weakness and muscle atrophy were present by 7 weeks of age in some puppies and evident to most owners by 14 weeks of age. Affected puppies stood with an arched spine and low head carriage, and walked with a short, choppy stride. Muscle atrophy was severe and progressive. Patellar reflexes were absent. Laryngeal and esophageal dysfunction, and weakness of the masticatory muscles occurred in puppies surviving beyond 4 months of age. Serum creatine kinase activity was normal or only mildly increased. EMG findings were nonspecific and included positive sharp waves and fibrillation potentials. Clinical signs progressed rapidly, with most affected puppies unable to walk within 3-4 weeks after clinical signs were first noticed. CONCLUSIONS AND CLINICAL IMPORTANCE: Although initial clinical signs of XLMTM are similar to the phenotypically milder centronuclear myopathy in Labrador Retrievers, XLMTM is a rapidly progressive and fatal myopathy. Clinicians should be aware of these 2 distinct myopathies with similar clinical presentations in the Labrador retriever breed.

Prospective evaluation of laparoscopic pancreatic biopsies in 11 healthy cats.

BACKGROUND: Definitive diagnosis of feline pancreatic disease is dependent on histologic examination of biopsies. HYPOTHESIS: Laparoscopic punch biopsy of the pancreas does not significantly affect pancreatic health or clinical status of healthy cats, and provides an adequate biopsy sample for histopathology. ANIMALS: Eleven healthy female domestic shorthair cats. METHODS: Effects of laparoscopic pancreatic visualization alone in 5 cats compared with laparoscopic pancreatic visualization and punch biopsy in 6 cats were studied. Temperature, pulse, and respiratory rate, physical examination, and daily caloric intake were evaluated for 1 week before and 1 week after the procedure. Pain scores (simple descriptive score and dynamic interactive visual assessment score) were evaluated hourly during the 1st 6 hours postprocedure. Complete blood cell counts, serum biochemical profiles, serum feline pancreatic lipase immunoreactivity, and urine specific gravity were evaluated before the procedure and at 6, 24, and 72 hours postprocedure. One month postprocedure, during sterilization, the pancreas was reassessed visually in all cats, and microscopically in the biopsy group. RESULTS: For all variables evaluated, there were no significant differences between biopsy and control cats. Re-evaluation of the pancreatic biopsy site 1 month later documented a normal tissue response to biopsy. The laparoscopic punch biopsy forceps provided high-quality pancreatic biopsy samples with an average size of 5 mm x 4 mm on 2-dimensional cut section. CONCLUSIONS AND CLINICAL IMPORTANCE: Laparoscopic pancreatic biopsy is a useful and safe technique in healthy cats.

Thrombin induces IL-6 but not TNFalpha secretion by mouse mast cells: threshold-level thrombin receptor and very low level FcepsilonRI signaling synergistically enhance IL-6 secretion.

Mast cells become activated in multiple diseases wherein thrombin generation is often clinically apparent, but the effect of thrombin on cytokine release by mast cells remains unexplored. Thus, we examined IL-6 and TNFalpha release by thrombin-challenged mast cells. Thrombin and the protease-activated receptor (PAR)-1 peptide TRAP(14) induced these cells to secrete IL-6 in a dose-dependent fashion. Mast cells secreted > or =2800 pg IL-6/10(6) cells over 24 h, but only low levels of serotonin and no significant TNFalpha. Furthermore, at near-background levels of allergen, threshold doses of alpha-thrombin synergistically enhanced the IL-6 response (by up to 100-fold), but high-dose costimulation led to a simple additive response. Both the PI(3)- and sphingosine-kinase signaling pathways contributed importantly to the thrombin response. Our data thus clearly demonstrate that low-level thrombin and FcepsilonRI signaling can synergize to augment mast cell IL-6 responses, and that thrombin also differentially induces cytokine secretion by mast cells.