title: Extreme Beta-Cell Deficiency in Pancreata of Dogs with Canine Diabetes.
abstract: The pathophysiology of canine diabetes remains poorly understood, in part due to enigmatic clinical features and the lack of detailed histopathology studies. Canine diabetes, similar to human type 1 diabetes, is frequently associated with diabetic ketoacidosis at onset or after insulin omission. However, notable differences exist. Whereas human type 1 diabetes often occurs in children, canine diabetes is typically described in middle age to elderly dogs. Many competing theories have been proposed regarding the underlying cause of canine diabetes, from pancreatic atrophy to chronic pancreatitis to autoimmune mediated β-cell destruction. It remains unclear to what extent β-cell loss contributes to canine diabetes, as precise quantifications of islet morphometry have not been performed. We used high-throughput microscopy and automated image processing to characterize islet histology in a large collection of pancreata of diabetic dogs. Diabetic pancreata displayed a profound reduction in β-cells and islet endocrine cells. Unlike humans, canine non-diabetic islets are largely comprised of β-cells. Very few β-cells remained in islets of diabetic dogs, even in pancreata from new onset cases. Similarly, total islet endocrine cell number was sharply reduced in diabetic dogs. No compensatory proliferation or lymphocyte infiltration was detected. The majority of pancreata had no evidence of pancreatitis. Thus, canine diabetes is associated with extreme β-cell deficiency in both new and longstanding disease. The β-cell predominant composition of canine islets and the near-total absence of β-cells in new onset elderly diabetic dogs strongly implies that similar to human type 1 diabetes, β-cell loss underlies the pathophysiology of canine diabetes.
authors.affiliation: McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, United States of America.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Shields
authors.affiliation: McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, United States of America.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Lam
authors.affiliation: McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, United States of America.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Cox
authors.affiliation: Pediatric Endocrinology and Diabetes, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Rankin
authors.affiliation: Matthew J. Ryan Veterinary Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Van Winkle
authors.affiliation: Matthew J. Ryan Veterinary Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
authors.forename: Rebecka S
authors.initials: RS
authors.lastname: Hess
authors.affiliation: McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, United States of America.
authors.forename: Jake A
authors.initials: JA
authors.lastname: Kushner
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000473:pathology / Q000662:veterinary*; D004285:Dogs; D005260:Female; D005934:Glucagon / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications / Q000473:pathology / Q000662:veterinary; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000473:pathology*; D007662:Ketosis / Q000150:complications / Q000473:pathology / Q000662:veterinary; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D009929:Organ Size
chemical_list: D007328:Insulin; D005934:Glucagon