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      A tale of two pancreases: exocrine pathology and endocrine dysfunction

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          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.

          Summary

          • Islets in context: Pancreatic islets exist within the exocrine pancreas, but the role of interactions between the exocrine and endocrine pancreas in determining normal islet health and function is poorly understood.

          • Pancreatogenic diabetes: A diverse array of exocrine pancreas diseases results in impaired insulin release and, ultimately, diabetes, providing evidence that endocrine/exocrine interactions are indeed critical for normal islet function.

          • Clues to underlying mechanisms: The underlying causes of the various forms of pancreatogenic diabetes are poorly understood, but emerging data highlight the importance of paracrine interactions between ductal epithelial cells and beta cells and/or islet inflammation.

          • Therapeutic considerations: Current treatment options for pancreatogenic diabetes are limited. Better understanding of diabetes-causing mechanisms is needed to develop diabetes prevention strategies and improved treatment approaches in these populations.

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          Author and article information

          Journal
          0006777
          3399
          Diabetologia
          Diabetologia
          Diabetologia
          0012-186X
          1432-0428
          23 October 2020
          07 September 2020
          October 2020
          06 November 2020
          : 63
          : 10
          : 2030-2039
          Affiliations
          [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
          Author notes

          Contribution statement

          All authors developed the outline of the article, reviewed and discussed the relevant literature, and were responsible for drafting the article and revising it critically for important intellectual content. All authors approved the version to be published.

          Correspondence to: Rebecca L. Hull, VA Puget Sound Health Care System (151), 1660 S. Columbian Way, Seattle, WA 98108, USA, rhull@ 123456uw.edu
          Article
          PMC7646259 PMC7646259 7646259 nihpa1639635
          10.1007/s00125-020-05210-8
          7646259
          32894313
          a0cee95d-7acd-4887-b100-0b864f519e22
          Categories
          Article

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