Evaluation of trypsin-like immunoreactivity, pancreatic lipase immunoreactivity, cobalamin, and folate in zoo-housed African painted dogs (Lycaon pictus) at a North American zoological facility.

OBJECTIVE: Assess markers for pancreatic function and gastrointestinal malabsorption in African painted dogs (Lycaon pictus), including canine trypsin-like immunoreactivity (cTLI), canine pancreatic lipase immunoreactivity (cPLI), cobalamin, and folate at one North American facility. ANIMALS: 15 healthy African painted dogs held at one institution were sampled during routine health examinations. METHODS: Blood was collected at routine health examinations, and serum was separated and stored until testing. Serum was analyzed for cTLI, cPLI, cobalamin, and folate. The results were evaluated for correlation to sex, age, and storage time of samples. RESULTS: All individuals had cTLI and folate levels below normal reference ranges for domestic dogs (< 5.0 µg/L and < 7.7 µg/L, respectively). Cobalamin values were within or above reported domestic dog ranges, and cPLI values were within range as well. No analytes were significantly influenced by sex or time in storage, while cTLI was positively correlated with age. CLINICAL RELEVANCE: cTLI and folate did not fall within normal domestic canid reference ranges in this population of healthy African painted dogs. Clinical interpretation of these values based on domestic canid recommendations would indicate clinical disease, which was not apparent in this population. Analytes for pancreatic function and malabsorption or gastrointestinal indicators, including cTLI, cPLI, and folate, in African painted dogs should be interpreted with caution when using domestic dog references ranges.

The Ras activator RasGRP3 mediates diabetes-induced embryonic defects and affects endothelial cell migration.

RATIONALE: Fetuses that develop in diabetic mothers have a higher incidence of birth defects that include cardiovascular defects, but the signaling pathways that mediate these developmental effects are poorly understood. It is reasonable to hypothesize that diabetic maternal effects are mediated by 1 or more pathways activated downstream of aberrant glucose metabolism, because poorly controlled maternal glucose levels correlate with the frequency and severity of the defects. OBJECTIVE: We investigated whether RasGRP3 (Ras guanyl-releasing protein 3), a Ras activator expressed in developing blood vessels, mediates diabetes-induced vascular developmental defects. RasGRP3 is activated by diacylglycerol, and diacylglycerol is overproduced by aberrant glucose metabolism in diabetic individuals. We also investigated the effects of overactivation and loss of function for RasGRP3 in primary endothelial cells and developing vessels. METHODS AND RESULTS: Analysis of mouse embryos from diabetic mothers showed that diabetes-induced developmental defects were dramatically attenuated in embryos that lacked Rasgrp3 function. Endothelial cells that expressed activated RasGRP3 had elevated Ras-ERK signaling and perturbed migration, whereas endothelial cells that lacked Rasgrp3 function had attenuated Ras-ERK signaling and did not migrate in response to endothelin-1. Developing blood vessels exhibited endothelin-stimulated vessel dysmorphogenesis that required Rasgrp3 function. CONCLUSIONS: These findings provide the first evidence that RasGRP3 contributes to developmental defects found in embryos that develop in a diabetic environment. The results also elucidate RasGRP3-mediated signaling in endothelial cells and identify endothelin-1 as an upstream input and Ras/MEK/ERK as a downstream effector pathway. RasGRP3 may be a novel therapeutic target for the fetal complications of diabetes.