Gilor Chen, Pires Jully, Greathouse Rachel, Horn Rebecca, Huising Mark O, Marks Stanley L, Murphy Brian, Kol Amir
Department of Veterinary Medicine and Epidemiology, College of Veterinary Medicine, University of California, One Shields Ave., Davis, CA, 95616, USA.
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, 2015 SW 16th Ave, Gainesville, FL, 32610, USA.
Sci Rep. 2020 Nov 5;10(1):19187. doi: 10.1038/s41598-020-76091-5.
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.
犬糖尿病（DM）影响0.6%的犬类群体，但其病因仍知之甚少。大多数患病犬在成年时被诊断出来，且依赖胰岛素。我们比较了患有自发性糖尿病（sDM）、自发性胰腺炎（sPanc）、两者皆有（sDMPanc）、毒素诱导性糖尿病（iDM）的成年犬以及对照犬的胰岛中的全白细胞和交感神经支配标记物。我们发现，在所有疾病组中，胰岛交感神经支配减少，但胰岛中没有明显的白细胞浸润。我们表明，在犬糖尿病中，交感神经支配的丧失是持续存在的，且不一定先于糖尿病发生。我们进一步发现，患有sDM和sDMPanc的犬中，胰岛相关β细胞有选择性丧失，这表明外分泌胰腺炎症的附带损害不太可能是这些犬患糖尿病的原因。β细胞这种选择性丧失的原因需要进一步阐明，但总体而言，我们的研究结果不支持自身免疫过程是成年犬sDM病因的观点。未患糖尿病的犬中sPanc的交感神经支配丧失将外分泌胰腺疾病与内分泌胰腺的病理过程联系起来，表明胰腺炎可能是糖尿病的潜在先兆。
