Disrupted pancreatic exocrine differentiation and malabsorption in response to chronic elevated systemic glucocorticoid.

The American Journal of Pathology
Karen WallaceMatthew C Wright

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 adu...Continue Reading

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Citations

Nov 16, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Philip M E ProbertMatthew C Wright
Jun 28, 2017·JBMR Plus·Jasmine Williams-DautovichCarolyn L Cummins
Aug 11, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Tarek M AbdelghanyMatthew C Wright

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