A tale of two pancreases: exocrine pathology and endocrine dysfunction
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REVIEW
A tale of two pancreases: exocrine pathology and endocrine dysfunction Michael R. Rickels 1,2
&
Andrew W. Norris 3,4
&
Rebecca L. Hull 5,6
Received: 2 April 2020 / Accepted: 14 May 2020 / Published online: 31 August 2020 # This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020
Abstract 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.
Keywords Cystic fibrosis . Diabetes . Exocrine . Islet . Pancreas . Pancreatitis . Review Abbreviations CEL Carboxyl-ester lipase CFTR Cystic fibrosis transmembrane conductance regulator
PP REG3A
Pancreatic polypeptide Regenerating family member 3α
Overview Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-020-05210-8) contains a slide of the figure for download, which is available to authorised users. * Rebecca L. Hull [email protected] 1
Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
2
Institute for Diabetes, Obesity & Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
3
Department of Pediatrics, University of Iowa, Iowa City, IA, USA
4
Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA
5
VA Puget Sound Health Care System (151), 1660 S. Columbian Way, Seattle, WA 98108, USA
6
Department of Medicine, University of Washington, Seattle, WA, USA
Under normal conditions, the exocrine (acinar and ductal) and endocrine pancreas co-exist in harmony (Fig. 1a,c). The organisation of these pancreatic compartments is the topic of some excellent reviews [1, 2] and is not covered here. The nature of the interactions between exocrine and endocrine pancreas and the role thereof
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