2017
DOI: 10.2337/db16-1551
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Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice, and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked?

Abstract: Despite decades of research in humans and mouse models of disease, substantial gaps remain in our understanding of pathogenic mechanisms underlying the development of type 1 diabetes. Furthermore, translation of therapies from preclinical efforts capable of delaying or halting β-cell destruction has been limited. Hence, a pressing need exists to identify alternative animal models that reflect human disease. Canine insulin deficiency diabetes is, in some cases, considered to follow autoimmune pathogenesis, simi… Show more

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Cited by 47 publications
(60 citation statements)
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“…In those cases, relative hypoinsulinemia was defined as a failure of insulin secretion in the face of SIRS‐induced hyperglycemia, suggesting a transient diabetes mellitus, which is rarely reported in horses. Type‐1 diabetes mellitus, more commonly diagnosed in humans or in dogs, is observed as a consequence of immune‐mediated damage to the endocrine pancreas whereas type‐2 diabetes mellitus develops after decreased pancreatic β cell function after sustained hyperinsulinemia . In 1 foal with severe SIRS, a transient type‐1 diabetes mellitus has been described suggesting that severe SIRS could lead to pancreatic dysfunction .…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…In those cases, relative hypoinsulinemia was defined as a failure of insulin secretion in the face of SIRS‐induced hyperglycemia, suggesting a transient diabetes mellitus, which is rarely reported in horses. Type‐1 diabetes mellitus, more commonly diagnosed in humans or in dogs, is observed as a consequence of immune‐mediated damage to the endocrine pancreas whereas type‐2 diabetes mellitus develops after decreased pancreatic β cell function after sustained hyperinsulinemia . In 1 foal with severe SIRS, a transient type‐1 diabetes mellitus has been described suggesting that severe SIRS could lead to pancreatic dysfunction .…”
Section: Discussionmentioning
confidence: 99%
“…Type-1 diabetes mellitus, more commonly diagnosed in humans or in dogs, is observed as a consequence of immune-mediated damage to the endocrine pancreas whereas type-2 diabetes mellitus develops after decreased pancreatic b cell function after sustained hyperinsulinemia. 42,43 In 1 foal with severe SIRS, a transient type-1 diabetes mellitus has been described suggesting that severe SIRS could lead to pancreatic dysfunction. 44 In agreement with those reports, our data indicate that severe hyperglycemia, in the face of an inadequate insulin response, is associated with non-survival and reflects a possible state of relative hypoinsulinemia or inappropriate lack of insulin secretion.…”
Section: Discussionmentioning
confidence: 99%
“…The pathogenesis of autoimmune diabetes is being extensively investigated in both humans and in animal models (9). Though the exact mechanisms that underlie autoimmune destruction of β cells remain elusive, it is generally believed that the disease process is triggered by the activation of autoreactive T cells by islet autoantigens, such as insulin, GAD65, IA2, and ZNT18.…”
Section: Autoimmune Destruction Of Pancreatic Islet β Cellsmentioning
confidence: 99%
“…Many unknowns still exist with respect to the pathogenesis of canine diabetes, and metabolomic alterations may represent important potential biomarkers to detect diabetes in dogs prior to clinical onset. Indeed, the ability to detect the pre-diabetic state may represent a key component to future discovery in this area 10 and to further define the utility of the dog as a potential model of human…”
Section: Studies Examining Inter-and Intra-individual Variability In mentioning
confidence: 99%