Subscribe to thousands of academic journals for just $40/month
Read and share the articles you need for your research, all in one place.

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

American Journal of Pathology , Volume 177 (3): 1225 – Sep 1, 2010

Details

Publisher
ASIP
Copyright
Copyright © 2010 by the American Society for Investigative Pathology.
ISSN
0002-9440
eISSN
1525-2191
D.O.I.
10.2353/ajpath.2010.100107
Publisher site
See Article on Publisher Site

Preview Only

Expand Tray Hide Tray

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

Abstract

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 transdifferentiation. 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 transdifferentiation 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.
Loading next page...

Preview Only. This article cannot be rented because we do not currently have permission from the publisher.

 
/lp/american-society-for-investigative-pathology/disrupted-pancreatic-exocrine-differentiation-and-malabsorption-in-mQndnSoTwk