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. 1984 Jun 1;98(6):2082–2090. doi: 10.1083/jcb.98.6.2082

Induction and origin of hepatocytes in rat pancreas

PMCID: PMC2113061  PMID: 6202703

Abstract

2-[4(2,2- Dichlorocyclopropyl )phenoxy]2-methyl propionic acid (ciprofibrate), a peroxisome proliferator , induced hepatocytes in the pancreas of adult male F-344 rats when added to their diet at a dosage of 10 mg/kg body weight for 60-72 wk. These cells are morphologically indistinguishable from hepatic hepatocytes and were usually localized adjacent to islets of Langerhans with extensions into surrounding acinar tissue. A significant increase in the volume density of peroxisomes, together with immunochemically detectable amounts of two peroxisome-associated enzymes, was observed in pancreas with hepatocytes of rats maintained on ciprofibrate. Uricase-containing crystalloid nucleoids, specific for rat hepatocyte peroxisomes, were present in pancreatic hepatocytes. These structures facilitated the identification of cells with hybrid cytoplasmic features characteristic of pancreatic acinar and endocrine cells and hepatocytes. Such cells are presumed to represent a transitional state in which pancreas specific genes are being repressed while liver specific ones are simultaneously expressed. The presence of exocrine and/or endocrine secretory granules in transitional cells indicates that acinar/intermediate cells represent the precursor cell from which pancreatic hepatocytes are derived.

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Selected References

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  1. Craddock V. M. Induction of liver tumours in rats by a single treatment with nitroso compounds given after partial hepatectomy. Nature. 1973 Oct 19;245(5425):386–389. doi: 10.1038/245386a0. [DOI] [PubMed] [Google Scholar]
  2. FITZGERALD P. J. The problem of the precursor cell of regenerating pancreatic acinar epithelium. Lab Invest. 1960 Jan-Feb;9:67–85. [PubMed] [Google Scholar]
  3. Goldfischer S., Villaverde H., Forschirm R. The demonstration of acid hydrolase, thermostable reduced diphosphopyridine nucleotide tetrazolium reductase and peroxidase activities in human lipofuscin pigment granules. J Histochem Cytochem. 1966 Sep;14(9):641–652. doi: 10.1177/14.9.641. [DOI] [PubMed] [Google Scholar]
  4. HRUBAN Z., SWIFT H. URICASE: LOCALIZATION IN HEPATIC MICROBODIES. Science. 1964 Dec 4;146(3649):1316–1318. doi: 10.1126/science.146.3649.1316. [DOI] [PubMed] [Google Scholar]
  5. Hess R., Stäubli W., Riess W. Nature of the hepatomegalic effect produced by ethyl-chlorophenoxy-isobutyrate in the rat. Nature. 1965 Nov 27;208(5013):856–858. doi: 10.1038/208856a0. [DOI] [PubMed] [Google Scholar]
  6. Holtzer H., Weintraub H., Mayne R., Mochan B. The cell cycle, cell lineages, and cell differentiation. Curr Top Dev Biol. 1972;7:229–256. doi: 10.1016/s0070-2153(08)60073-3. [DOI] [PubMed] [Google Scholar]
  7. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  8. Lalwani N. D., Fahl W. E., Reddy J. K. Detection of a nafenopin-binding protein in rat liver cytosol associated with the induction of peroxisome proliferation by hypolipidemic compounds. Biochem Biophys Res Commun. 1983 Oct 31;116(2):388–393. doi: 10.1016/0006-291x(83)90534-x. [DOI] [PubMed] [Google Scholar]
  9. Lalwani N. D., Reddy M. K., Mangkornkanok-Mark M., Reddy J. K. Induction, immunochemical identity and immunofluorescence localization of an 80 000-molecular-weight peroxisome-proliferation-associated polypeptide (polypeptide PPA-80) and peroxisomal enoyl-CoA hydratase of mouse liver and renal cortex. Biochem J. 1981 Jul 15;198(1):177–186. doi: 10.1042/bj1980177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lalwani N. D., Reddy M. K., Qureshi S. A., Sirtori C. R., Abiko Y., Reddy J. K. Evaluation of selected hypolipidemic agents for the induction of peroxisomal enzymes and peroxisome proliferation in the rat liver. Hum Toxicol. 1983 Jan;2(1):27–48. doi: 10.1177/096032718300200103. [DOI] [PubMed] [Google Scholar]
  11. Lazarow P. B. Rat liver peroxisomes catalyze the beta oxidation of fatty acids. J Biol Chem. 1978 Mar 10;253(5):1522–1528. [PubMed] [Google Scholar]
  12. Leighton F., Poole B., Lazarow P. B., De Duve C. The synthesis and turnover of rat liver peroxisomes. I. Fractionation of peroxisome proteins. J Cell Biol. 1969 May;41(2):521–535. doi: 10.1083/jcb.41.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. MARGOLIASH E., NOVOGRODSKY A., SCHEJTER A. Irreversible reaction of 3-amino-1:2:4-triazole and related inhibitors with the protein of catalase. Biochem J. 1960 Feb;74:339–348. doi: 10.1042/bj0740339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Melmed R. N., Benitez C. J., Holt S. J. Intermediate cells of the pancreas. I. Ultrastructural characterization. J Cell Sci. 1972 Sep;11(2):449–475. doi: 10.1242/jcs.11.2.449. [DOI] [PubMed] [Google Scholar]
  15. Moody D. E., Reddy J. K. Morphometric analysis of the ultrastructural changes in rat liver induced by the peroxisome proliferator SaH 42-348. J Cell Biol. 1976 Dec;71(3):768–780. doi: 10.1083/jcb.71.3.768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Novikoff A. B., Novikoff P. M., Davis C., Quintana N. Studies on microperoxisomes. V. Are microperoxisomes ubiquitous in mammalian cells? J Histochem Cytochem. 1973 Aug;21(8):737–755. doi: 10.1177/21.8.737. [DOI] [PubMed] [Google Scholar]
  17. Osumi T., Hashimoto T. Peroxisomal beta oxidation system of rat liver. Copurification of enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase. Biochem Biophys Res Commun. 1979 Jul 27;89(2):580–584. doi: 10.1016/0006-291x(79)90669-7. [DOI] [PubMed] [Google Scholar]
  18. Rao M. S., Reddy M. K., Reddy J. K., Scarpelli D. G. Response of chemically induced hepatocytelike cells in hamster pancreas to methyl clofenapate, a peroxisome proliferator. J Cell Biol. 1982 Oct;95(1):50–56. doi: 10.1083/jcb.95.1.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rao M. S., Subbarao V., Luetteke N., Scarpelli D. G. Further characterization of carcinogen-induced hepatocytelike cells in hamster pancreas. Am J Pathol. 1983 Jan;110(1):89–94. [PMC free article] [PubMed] [Google Scholar]
  20. Reddy J. K., Krishnakantha T. P. Hepatic peroxisome proliferation: induction by two novel compounds structurally unrelated to clofibrate. Science. 1975 Nov 21;190(4216):787–789. doi: 10.1126/science.1198095. [DOI] [PubMed] [Google Scholar]
  21. Reddy J. K., Kumar N. S. The peroxisome proliferation-associated polypeptide in rat liver. Biochem Biophys Res Commun. 1977 Aug 8;77(3):824–829. doi: 10.1016/s0006-291x(77)80052-1. [DOI] [PubMed] [Google Scholar]
  22. Reddy J. K., Lalwani N. D., Reddy M. K., Qureshi S. A. Excessive accumulation of autofluorescent lipofuscin in the liver during hepatocarcinogenesis by methyl clofenapate and other hypolipidemic peroxisome proliferators. Cancer Res. 1982 Jan;42(1):259–266. [PubMed] [Google Scholar]
  23. Reddy J. K., Warren J. R., Reddy M. K., Lalwani N. D. Hepatic and renal effects of peroxisome proliferators: biological implications. Ann N Y Acad Sci. 1982;386:81–110. doi: 10.1111/j.1749-6632.1982.tb21409.x. [DOI] [PubMed] [Google Scholar]
  24. Scarpelli D. G., Rao M. S. Differentiation of regenerating pancreatic cells into hepatocyte-like cells. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2577–2581. doi: 10.1073/pnas.78.4.2577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shnitka T. K. Comparative ultrastructure of hepatic microbodies in some mammals and birds in relation to species differences in uricase activity. J Ultrastruct Res. 1966 Dec;16(5):598–625. doi: 10.1016/s0022-5320(66)80009-6. [DOI] [PubMed] [Google Scholar]
  26. Svoboda D., Grady H., Azarnoff D. Microbodies in experimentally altered cells. J Cell Biol. 1967 Oct;35(1):127–152. doi: 10.1083/jcb.35.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tandler B., Erlandson R. A., Smith A. L., Wynder E. L. Riboflavin and mouse hepatic cell structure and function. II. Division of mitochondria during recovery from simple deficiency. J Cell Biol. 1969 May;41(2):477–493. doi: 10.1083/jcb.41.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tsukada H., Mochizuki Y., Fujiwara S. The nucleoids of rat liver cell microbodies. Fine structure and enzymes. J Cell Biol. 1966 Mar;28(3):449–460. doi: 10.1083/jcb.28.3.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Weibel E. R. Stereological principles for morphometry in electron microscopic cytology. Int Rev Cytol. 1969;26:235–302. doi: 10.1016/s0074-7696(08)61637-x. [DOI] [PubMed] [Google Scholar]

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