Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Institute for Diabetes, Obesity & Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Diabetologia. 2020 Oct;63(10):2030-2039. doi: 10.1007/s00125-020-05210-8. Epub 2020 Sep 7.
The islets of Langerhans are well embedded within the exocrine pancreas (the latter comprised of ducts and acini), but the nature of interactions between these pancreatic compartments and their role in determining normal islet function and survival are poorly understood. However, these interactions appear to be critical, as when pancreatic exocrine disease occurs, islet function and insulin secretion frequently decline to the point that diabetes ensues, termed pancreatogenic diabetes. The most common forms of pancreatogenic diabetes involve sustained exocrine disease leading to ductal obstruction, acinar inflammation, and fibro-fatty replacement of the exocrine pancreas that predates the development of dysfunction of the endocrine pancreas, as seen in chronic pancreatitis-associated diabetes and cystic fibrosis-related diabetes and, more rarely, MODY type 8. Intriguingly, a form of tumour-induced diabetes has been described that is associated with pancreatic ductal adenocarcinoma. Here, we review the similarities and differences among these forms of pancreatogenic diabetes, with the goal of highlighting the importance of exocrine/ductal homeostasis for the maintenance of pancreatic islet function and survival and to highlight the need for a better understanding of the mechanisms underlying these diverse conditions. Graphical abstract.
胰岛被很好地嵌入外分泌胰腺（后者由导管和腺泡组成）中，但这些胰腺部分之间的相互作用的性质及其在外分泌腺疾病发生时，胰岛功能和胰岛素分泌通常会下降到导致糖尿病发生的正常胰岛功能和存活中的作用仍知之甚少。这些相互作用似乎至关重要，正如当发生胰腺外分泌疾病时，称为胰源性糖尿病。最常见的胰源性糖尿病形式涉及持续的外分泌疾病导致导管阻塞、腺泡炎症和纤维脂肪替代外分泌胰腺，这先于内分泌胰腺功能障碍的发展，如慢性胰腺炎相关糖尿病和囊性纤维化相关糖尿病，以及更罕见的 MODY 类型 8。有趣的是，已经描述了一种与胰腺导管腺癌相关的肿瘤诱导性糖尿病。在这里，我们回顾了这些胰源性糖尿病形式的相似之处和不同之处，目的是强调外分泌/导管动态平衡对于维持胰腺胰岛功能和存活的重要性，并强调需要更好地理解这些不同疾病的机制。
