Loss of sympathetic innervation to islets of Langerhans in canine diabetes and pancreatitis is not associated with insulitis

Abstract

Canine diabetes mellitus (DM) affects 0.6% of the canine population and yet, its etiology is poorly understood. Most affected dogs are diagnosed as adults and are insulin-dependent. We compared pan-leukocyte and sympathetic innervation markers in pancreatic islets of adult dogs with spontaneous DM (sDM), spontaneous pancreatitis (sPanc), both (sDMPanc), toxin-induced DM (iDM) and controls. We found evidence of decreased islet sympathetic innervation but no significant infiltration of islets with leukocytes in all disease groups. We show that loss of sympathetic innervation is ongoing in canine DM and does not necessarily precede it. We further found selective loss of islet-associated beta cells in dogs with sDM and sDMPanc, suggesting that collateral damage from inflammation in the exocrine pancreas is not a likely cause of DM in these dogs. The cause of this selective loss of beta cells needs to be further elucidated but overall, our findings are not supportive of an autoimmune process as a cause of sDM in adult dogs. The loss of sympathetic innervation in sPanc in dogs that do not suffer from DM links the disease in the exocrine pancreas to a pathological process in the endocrine pancreas, suggesting pancreatitis might be a potential precursor to DM.

Fenofibrate promotes PPARα-targeted recovery of the intestinal epithelial barrier at the host-microbe interface in dogs with diabetes mellitus

“…Seven male, 1.5-year-old beagles (weighing 7.3–11.7 kg) were housed individually with free access to drinking water and supervised access to outdoor play pens. Diabetes was induced with alloxan and streptozotocin, as previously described 15 , 8 months before this study. During the 8 weeks preceding the study, dogs were treated with ~ 0.7 U/kg porcine zinc insulin suspension (Vetsulin®, Merck Animal Health, Madison, NJ) at the time of their evening meal.…”

Day‐to‐day variability of porcine lente, insulin glargine 300 U/mL and insulin degludec in diabetic dogs

“…In human medicine, increased GV is used as a predictor of future hypoglycemic events, 21‐23 but to the best of our knowledge, has not been studied in dogs. However, because the mechanisms leading to impaired counterregulatory responses in dogs are largely the same as in people, 24 it would be reasonable to hypothesize that as in people, increased GV in dogs would also lead to increased frequency of hypoglycemia in the long run.…”

Serum trypsin‐like immunoreactivity in dogs with diabetes mellitus

“…4 However, evidence for autoimmunity in DM in dogs is inconsistent and it is now recognized to be a heterogeneous syndrome. [5][6][7][8] Other factors that might contribute to the development of DM in dogs include other endocrinopathies, exogenous steroid or progesterone administration, and exocrine pancreatic disorders such as pancreatitis. 6,9,10 Diabetes mellitus in humans is a disease of the entire pancreas, with exocrine pancreatic involvement occurring as either a cause or effect of T1DM.…”

“… 4 However, evidence for autoimmunity in DM in dogs is inconsistent and it is now recognized to be a heterogeneous syndrome. 5 , 6 , 7 , 8 Other factors that might contribute to the development of DM in dogs include other endocrinopathies, exogenous steroid or progesterone administration, and exocrine pancreatic disorders such as pancreatitis. 6 , 9 , 10 …”

“…Diabetes mellitus in dogs is often compared to human type 1 DM (T1DM), 3 a condition of absolute insulin deficiency characterized by islet‐directed autoimmunity 4 . However, evidence for autoimmunity in DM in dogs is inconsistent and it is now recognized to be a heterogeneous syndrome 5‐8 . Other factors that might contribute to the development of DM in dogs include other endocrinopathies, exogenous steroid or progesterone administration, and exocrine pancreatic disorders such as pancreatitis 6,9,10 …”