Streptozotocin-induced Functioning Islet Cell Tumor in the Rat: High Frequency of Induction and Biological Properties of the Tumor Cells

Abstract

After a long latency, hormone-producing islet cell tumors are induced with high frequency by a single administration of streptozotocin and nicotinamide in the rats. Thus, pancreatic islets must be considered a target tissue for the tumorigenic, as well as diabetogenic, action of streptozotocin. These tumors are well-differentiated and resemble normal islet tissue, both morphologically and functionally, as they are rich in typical β cells and release insulin in response to glucose, both in vivo and in culture. However, some noteworthy differences have been observed in comparison to normal tissue: (a) the release of large amounts of proinsulin after glucose stimulation, (b) the presence of granulated cells of uncertain classification, similar but not identical, to δ cells, and (c) the altered proportion in hormone content, which suggests a different sensitivity of the different islet cell types to the chemically induced transformation.

References

1. Rerup CC (1970). Drugs producing diabetes through damage of the insulin secreting cells. Pharmacol. Rev. 22: 485–518.

2. Rakieten N , Gordon BS , Beaty A , Cooney DA , Davis RD , and Schein PS (1971). Pancreatic islet cell tumors produced by the combined action of streptozotocin and nicotinamide. Proc. Soc. Exp. Biol. Med. 137: 280–283.

3. Dixit PK and Bauer GE (1976). Studies on rats with islet β cell tumors induced by nicotinamide and streptozotocin. Proc. Soc. Exp. Biol. Med. 152: 232–236.

4. Kazumi T , Yoshino G , Fujii S , and Baba S (1978). Tumorigenic action of streptozotocin on the pancreas and kidney in male Wistar rats. Cancer Res. 38: 2144–2147.

5. Masiello P , Karunanayake EH , Bergamini E , Hearse DJ , and Mellows G (1981). [14C]Streptozotocin: its distribution and interaction with nucleic acids and proteins. Diochem. Pharmacol 30: 1907–1913.

6. Bennett RA and Pegg AE (1981). Alkylation of DNA in rat tissues following administration of streptozotocin. Cancer Res. 41: 2786–2790.

7. Kenny J (1955). Extractable glucagon of the human pancreas. J. Clin. Endocrinol. 15: 865–871.

8. Meda P , Hooghe-Peters EL , and Orci L (1980). Monolayer cultures of adult pancreatic islet cells on osmotically disrupted fibroblasts. Diabetes 23. 497–500.

9. Herbert V , Lau K-S , Gottlieb CW , and Bleicher SJ (1965). Coated charcoal immunoassay of insulin. J. Clin. Endocrinol. 25: 1375–1384.

10.

10. Gerber PPG , Trimble ER , Wollheim CB , Renold AE , and Miller RE (1981). Glucose and cyclic AMP as stimulators of somatostatin and insulin secretion from the isolated, perfused rat pancreas: a quantitative study. Diabetes 30: 40–44.

11.

11. Fisher RA and Yates F (1963). Statistical Tables for Biological, Agricultural and Medical Research. 6th ed, Longmans, London.

12.

12. Orci L (1982). Macro- and microdomains in the endocrine pancreas. Diabetes 31: 538–565.

13.

13. Chick WL , Appel MC , Weir GC , Like AA , Lauris V , Porter JG , and Chute RN (1980). Serially transplant-able chemically induced rat islet cell tumor. Endocrinology 107: 954–960.

14.

14. Karunanayake EH , Baker JRJ , Christian RA , Hearse DJ , and Mellows G (1976). Autoradiographic study of the distribution and cellular uptake of [MC]streptozotocin in the rat. Diabetologia 12: 123–12B.

15.

15. Masiello P . Wollheim CB , Blondel B , and Renold AE (1983). Studies in vivo and in vitro on chemically induced primary islet cell tumors and non-tumor endocrine pancreatic tissue. Diabetologia 24: 30–37.

16.

16. Masiello P , Wollheim CB , Janjic D , Gjinovci A , Blondel B , Praz GA , and Renold AE (1982). Stimulation of insulin release by glucose in a transplant-able rat islet cell tumor. Endocrinology 111: 2091–2096.

17.

17. Berger M , Bordi C , CÜppers HJ , Berchtold P , Gries FA , Münterfering H , Sailer R , Zimmermann H , and Orci L (1983). Functional and morphologic characterization of human insulinomas. Diabetes 32: 921–931.

18.

18. Bordi C and Tardini A (1980). Electron microscopy of islet cell tumors. In: Progress in Surgical Pathology, CM Fenoglio , and M Wolff (eds). Masson, New York, pp. 135–155.

19.

19. Creutzfeldt W , Arnold R , Creutzfeldt C . Deuticke U , Frerichs H , and Track NS (1973). Biochemical and morphological investigations of 30 human insulinomas. Diabetologia 9: 217–231.