Hepatocyte-like Cells within the Pancreas of Rats Fed Methyl-Deficient Diets

Abstract

Administration of a methyl-group-deficient diet with or without an initial single injection of diethylnitrosamine to male Fischer 344 rats resulted in the development of cells structurally similar to hepatocytes that lay in small clusters around one or more islets of Langerhans in the pancreas. These cells were detected in 15/256 rats fed various methyl-deficient diets in study 1 and in 7/28 rats fed a severely methyl-group-deficient diet in study 2. The results of special staining procedures for the detection of glycogen, albumin and particulate iron uptake indicated that at least some of these cells shared features common to liver cells. These results, as well as previously reported observations of similar cells in hamsters treated with ethionine, provide additional evidence that the lack of available physiological methyl donors contributes to altered differentiation of pancreatic acinar cells.

Androgen regulated expression of the alpha 2u-globulin gene in pancreatic hepatocytes of rat.

“…Transdifferentiation of pancreatic ceils to hepatocytes in the pancreas of rats and hamsters has been observed under various experimental conditions (4,8,15,22,23,24,26,27,33). The copper depletion and repletion model of pancreatic hepatocytes (26,28) uses copper-deficient diet (20) supplemented with trien, a mild nontoxic copper chelator (35).…”

Epigenetics and Pancreatic Cancer: The Role of Nutrigenomics

“…Studies have shown that chronic administration of methionine-and choline-deficients diets results in global hypomethylation of hepatic DNA and development of spontaneous tumor formation (108). In those studies when the pancreas was examined in the methionine-and choline-deficients diets, a transdifferentiated (hepatocyte-like) phenotype was observed (109). The progentic of these cells have now been identified as pancreatic stem cells (PSCs) that are capable of producing cells with multiple markers of other non-pancreatic organs (110).…”

Immunohistochemical Evidence of High Concentrations of Metallothionein in Pancreatic Hepatocytes Induced by Cadmium in Rats

“…Transdifferentiation or metaplasia of rodent pancreatic cells into hepatocytes has been shown with several agents and treatments, including various organic carcinogens (8,15,16) and dietary deficiencies of copper ( 13) and methionine (6). Cadmium, a toxic and carcinogenic heavy metal (20), was recently found in our laboratory to be highly effective in inducing pancreatic hepatocyte formation in both Wistar [WF/NCr] and Fischer [F344/NCr] rats (7).…”

“…It has been suggested that hypomethylation of DNA, which can allow the expression of various genes otherwise only modestly expressed (5,14), may be generally involved in pancreatic transdifferentiation induced by several treatments (6). Thus, hypomethylation of DNA is thought to be involved in pancreatic hepatocyte formation resulting from feeding of methionine-deficient diets and possibly from copper-deficient diets (6) …”

“…Thus, hypomethylation of DNA is thought to be involved in pancreatic hepatocyte formation resulting from feeding of methionine-deficient diets and possibly from copper-deficient diets (6) …”