Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Sydney School of Veterinary Science, Faculty of Science, The University of Sydney, Sydney, Australia.
Stem Cells Transl Med. 2019 May;8(5):450-455. doi: 10.1002/sctm.18-0163. Epub 2019 Feb 5.
Diabetes mellitus (DM) is a common spontaneous endocrine disorder in dogs, which is defined by persistent hyperglycemia and insulin deficiency. Like type 1 diabetes (T1D) in people, canine DM is a complex and multifactorial disease in which genomic and epigenomic factors interact with environmental cues to induce pancreatic β-cell loss and insulin deficiency, although the pathogenesis of canine DM is poorly defined and the role of autoimmunity is further controversial. Both diseases are incurable and require life-long exogenous insulin therapy to maintain glucose homeostasis. Human pancreatic islet physiology, size, and cellular composition is further mirrored by canine islets. Although pancreatic or isolated islets transplantation are the only clinically validated methods to achieve long-term normoglycemia and insulin independence, their availability does not meet the clinical need; they target a small portion of patients and have significant potential adverse effects. Therefore, providing a new source for β-cell replacement is an unmet need. Naturally occurring DM in pet dogs, as a translational platform, is an untapped resource for various regenerative medicine applications that may offer some unique advantages given dogs' large size, longevity, heterogenic genetic background, similarity to human physiology and pathology, and long-term clinical management. In this review, we outline different strategies for curative approaches, animal models used, and consider the value of canine DM as a translational animal/disease model for T1D in people. Stem Cells Translational Medicine 2019;8:450-455.
糖尿病（DM）是犬常见的自发性内分泌紊乱疾病，其特征为持续高血糖和胰岛素缺乏。与人类 1 型糖尿病（T1D）一样，犬 DM 是一种复杂的多因素疾病，其中基因组和表观基因组因素与环境线索相互作用，导致胰岛 β 细胞损失和胰岛素缺乏，尽管犬 DM 的发病机制尚未明确，自身免疫的作用仍存在争议。这两种疾病均无法治愈，需要终身外源性胰岛素治疗来维持血糖稳态。人类胰岛的生理学、大小和细胞组成与犬胰岛进一步相似。虽然胰腺或分离胰岛移植是实现长期正常血糖和胰岛素独立性的唯一经临床验证的方法，但它们的可用性无法满足临床需求；它们仅适用于一小部分患者，且具有显著的潜在不良反应。因此，提供新的β细胞替代来源是一个未满足的需求。宠物犬中自然发生的 DM 作为一种转化平台，是各种再生医学应用的未开发资源，鉴于犬体型较大、寿命较长、遗传背景多样化、与人类生理学和病理学相似，以及长期临床管理，这些应用可能具有一些独特的优势。在这篇综述中，我们概述了不同的治疗策略、所用动物模型，并考虑了犬 DM 作为人类 T1D 转化动物/疾病模型的价值。Stem Cells Translational Medicine 2019;8:450-455.
