Abstract
While predominant as a disease entity, knowledge voids exist regarding the pathogenesis of canine diabetes. To test the hypothesis that diabetic dogs have similar metabolomic perturbations to humans with type 1 diabetes (T1D), we analyzed serum metabolomic profiles of breed- and body weight-matched, diabetic (n = 6) and healthy (n = 6) dogs by liquid chromatography-mass spectrometry (LC-MS) profiling. We report distinct clustering of diabetic and control groups based on heat map analysis of known and unknown metabolites. Random forest classification identified 5/6 dogs per group correctly with overall out of bag error rate = 16.7%. Diabetic dogs demonstrated significant upregulation of glycolysis/gluconeogenesis intermediates (e.g., glucose/fructose, C6H12O6, keto-hexose, deoxy-hexose, (P < 0.01)), with significant downregulation of tryptophan metabolism metabolites (e.g., picolinic acid, indoxyl sulfate, anthranilate, (P < 0.01)). Multiple amino acids (AA), AA metabolites, and bile acids were also significantly lower in diabetic versus healthy dogs (P < 0.05) with the exception of the branched chain AA valine, which was elevated in diabetic animals (P < 0.05). Metabolomic profiles in diabetic versus healthy dogs shared similarities with those reported in human T1D (e.g., alterations in glycolysis/gluconeogensis metabolites, bile acids, and elevated branched chain AA). Further studies are warranted to evaluate the utility of canine diabetes to provide novel mechanistic insights to the human disorder.
Highlights
Type 1 diabetes (T1D) is characterized by insulin deficiency and resulting dysglycemia[1]
Further research is required to determine the potential for canines with diabetes to be used as an alternative animal model of human T1D10, and if metabolomic analysis may identify novel biomarkers of the disease
While metabolomic profiles have been studied in healthy dogs[11, 12] and in several disease states, including inflammatory bowel disease[13] and degenerative valvular disease14, 1Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Florida, Gainesville, Florida, USA. 2Department of Pathology, Immunology, and Laboratory Medicine, The University of Florida, Gainesville, Florida, USA
Summary
Type 1 diabetes (T1D) is characterized by insulin deficiency and resulting dysglycemia[1]. T1D patients with poor glycemic control demonstrate decreased glycolytic metabolites and elevated carbohydrate metabolites, branched chain amino acids (AA), short chain FA, and ketoacids[4]. Many of these metabolic perturbations are present in T1D patients with good glycemic control[4]. We evaluated the metabolomic profiles of fasted diabetic versus healthy control dogs, and hypothesized that diabetic dogs have metabolomic perturbations similar to those reported in human T1D patients, including alterations in carbohydrates, branched-chain AA and FA
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