Disrupted Pancreatic Exocrine Differentiation and Malabsorption in Response to Chronic Elevated Systemic Glucocorticoid

  1. Lookup NU author(s)
  2. Dr Karen Wallace
  3. Professor Paul Flecknell
  4. Professor Alastair Burt
  5. Professor Matthew Wright
Author(s)Wallace K, Flecknell PA, Burt AD, Wright MC
Publication type Article
JournalAmerican Journal of Pathology
Year2010
Volume177
Issue3
Pages1225-1232
ISSN (print)0002-9440
ISSN (electronic)1525-2191
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Glucocorticoids are antiinflammatory therapeutics that have potent effects on cell differentiation. The aim of this study was to establish whether systemic glucocorticoid exposure significantly affects pancreatic differentiation in vivo because hepatocyte-like cells have been documented to occur in the diseased rodent pancreas. Expression of hepatic markers was examined in pancreata from mice genetically modified to secrete elevated circulating endogenous glucocorticoid [Tg(Crh)]. Tg(Crh) mice with elevated glucocorticoid appeared cushingoid and by 21 weeks of age were obese, insulin-resistant, and had extensive areas of hepatic gene expression in exocrine tissue. Acinar cells from Tg(Crh) mice costained for both amylase and cyp2e1, suggesting direct acinar-hepatic trans-differentiation. Hepatic expression increased with age in the pancreas to such an extent that malabsorption and rapid weight loss occurred in a subset of aging mice; this effect was reversed by dietary porcine pancreatic enzyme supplementation. Indeed, pancreatic expression of hepatic markers was prevented by adrenalectomy, establishing a direct role for glucocorticoid. Elevated levels of circulating glucocorticoid therefore promote a trans-differentiation of adult exocrine pancreas into hepatocyte-like cells , and chronic exposure results in pancreatic malfunction. Glucocorticoids are thus capable of modulating the differentiation of terminally differentiated adult cells.
PublisherAmerican Society for Investigative Pathology
URLhttp://dx.doi.org/10.2353/ajpath.2010.100107
DOI10.2353/ajpath.2010.100107
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