Summary
Rat islet cell tumours induced by injection of streptozotocin and nicotinamide have been studied in vivo and after the establishment of monolayer cultures of tumour cells. During an intravenous glucose tolerance test, tumour-bearing rats had increased release of immunoreactive insulin, with a high proportion of proinsulin, as well as accelerated glucose disposal relative to control rats. The tumours were rich in immunoreactive insulin and somatostatin, poor in glucagon. Non-tumour pancreatic tissue or isolated islets contained 10% or less of the corresponding normal amounts of insulin whereas the islet content of somatostatin was unchanged and that of glucagon increased. This is best interpreted as a selective suppression of non-tumour B cells, further supported by the observation that the initially reduced insulin release and content of non-tumour islets were partially restored after 2 days in tissue culture. In monolayer culture, tumour cells maintained insulin production and acute responsiveness to glucose for prolonged periods. There was no sign of cell proliferation. It is concluded that primary, chemically-induced insulin-producing pancreatic islet cell tumours retain several features characteristic of normal B cells and continue to influence glucose homeostasis in vivo.
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Rakieten N, Gordon BS, Beaty A, Cooney DA, Davis RD, Schein PS (1971) Pancreatic islet cell tumors produced by the combined action of streptozotocin and nicotinamide. Proc Soc Exp Biol Med 137: 280–283
Dixit PK, Bauer GE (1976) Studies on rats with islet beta cell tumors induced by nicotinamide and streptozotocin. Proc Soc Exp Biol Med 152: 232–236
Kazumi T, Yoshino G, Fujii S, Baba S (1978) Tumorigenic action of streptozotocin on the pancreas and kidney in male Wistar rats. Cancer Res 38: 2144–2147
Kazumi T, Yoshino G, Yoshida Y, Doi K, Yoshida M, Kaneko S, Baba S (1978) Biochemical studies on rats with insulin-secreting islet cell tumors induced by streptozotocin: with special reference to physiological response to oral glucose load in the course of and after tumor induction. Endocrinology 103: 1541–1545
Creutzfeldt W, Arnold R, Creutzfeldt C, Frerichs H (1980) Induction of hormone-producing pancreatic tumours in the rat. In: Andreani D, Lefebvre PS, Marks V (eds) Current views on hypoglycaemia and glucagon. Academic Press, London, New York pp 205–221
Frigo I, Younoszai R, Dixit PK, Matta SG, Bauer GE (1981) Insulin release in vitro from islet tissues and adenomas of rats treated with nicotinamide and streptozotocin. The effects of glucose. Diabetes 30: 302–309
Kazumi T, Sakamoto C, Ohki A, Yoshino G, Otsuki M, Baba S (1981) Insulin release from the isolated perfused rat pancreas containing insulinomata induced by streptozotocin and nicotinamide: effects of glucose and responses to tumor removal. Endocrinology 109: 607–610
Chick WL, Appel MC, Weir GC, Like AA, Lauris V, Porter JG, Chute RN (1980) Serially transplantable chemically induced rat islet cell tumors. Endocrinology 107: 954–960
Yoshino G, Utsumi M, Kazumi T, Makimura H, Ishihara K, Kobayashi N, Terashi K, Morita S, Baba S (1980) Pancreatic insulin, glucagon and somatostatin concentrations in rats with islet cell tumors induced by streptozotocin. Endocrinol Japon 27: 561–565
Meda P, Hooghe-Peters EL, Orci L (1980) Monolayer cultures of adult pancreatic islet cells on osmotically disrupted fibroblasts. Diabetes 23: 497–500
Lacy PE, Kostianovsky M (1967) Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16: 35–39
Kenny J (1955) Extractable glucagon of the human pancreas. J Clin Endocr 15: 865–871
Bergmeyer HU, Bernt E (1970) Methoden der Enzymatischen Analyse. Verlag Chemie, Weinheim, p 1172
Herbert V, Lau K-S, Gottlieb CW, Bleicher SJ (1965) Coated charcoal immunoassay of insulin. J Clin Endocr 25: 1375–1384
Gerber PPG, Trimble ER, Wollheim CB, Renold AE, 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
Halban PA, Wollheim CB, Blondel B, Renold AE (1980) Longterm exposure of isolated pancreatic islets to mannoheptulose: evidence for insulin degradation in the β-cell. Biochem Pharmacol 29: 2625–2633
Ribes G, Siegel EG, Wollheim CB, Renold AE, Sharp GWG(1981) Rapid changes in calcium content of rat pancreatic islets in response to glucose. Diabetes 30: 52–55
Rabinovitch A, Cuendet GS, Sharp GWG, Renold AE, Mintz DH (1978) Relation of insulin release to cyclic AMP content in rat pancreatic islets maintained in tissue culture. Diabetes 27: 766–773
Halban PA, Wollheim CB, Blondel B, Niesor E, Renold AE (1979) Perturbation of hormone storage and release induced by cyproheptadine in rat pancreatic islets in vitro. Endocrinology 104: 1096–1106
Schoental R (1975) Pancreatic islet-cell and other tumors in rats given heliotrine, a monoester pyrrolizidine alkaloid, and nicotinamide. Cancer Res 35: 2020–2024
Chick WL, Warren S, Chute RN, Like AA, Lauris V, Kitchen KC (1977) A transplantable insulinoma in the rat. Proc Natl Acad Sci USA 74: 628–632
Masiello P, Wollheim CB, Janjic D, Gjinovici A, Blondel B, Praz GA, Renold AE. Stimulation of insulin release by glucose in a transplantable rat islet cell tumor. Endocrinology (in press)
Trimble ER, Renold AE (1981) Ventral and dorsal areas of rat pancreas: islet hormone content and secretion. Am J Physiol 240: E422-E427
Creutzfeldt W, Arnold R, Creutzfeldt C, Deuticke U, Frerichs H, Track NS (1973) Biochemical and morphological investigations of 30 human insulinomas. Diabetologia 9: 217–231
Niesor EJ, Wollheim CB, Mintz DH, Blondel B, Renold AE, Weil R (1979) Establishment of rat pancreatic endocrine cell lines by infection with Simian virus 40. Biochem J 178: 559–568
Santerre RF, Cook RA, Crisel RMD, Sharp JD, Schmidt RJ, Williams DC, Wilson CP (1981) Insulin synthesis in a clonal cell line of Simian virus 40-transformed hamster pancreatic beta cells. Proc Natl Acad Sci USA 78: 4339–4343
Sodoyez J-C, Sodoyez-Goffaux F, Lefebvre PJ, Foà PP (1968) A transplantable insulinoma of the Syrian hamster mesocricetus auratus auratus. Review of its properties and of its effects on the host. Acta Diabetol Lat 5 (Suppl 1): 86–104
Dunbar JC, Walsh MF, Foà PP (1976) Secretion of immunoreactive insulin and glucagon in hamsters bearing a transplantable insulinoma. Diabete Metab 2:165–169
Junod A, Lambert AE, Stauffacher W, Renold AE (1969) Diabetogenic action of streptozotocin: relationship of dose to metabolic response. J Clin Invest 48: 2129–2139
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Masiello, P., Wollheim, C.B., Blondel, B. et al. Studies in vivo and in vitro on chemically-induced primary islet cell tumours and non-tumour endocrine pancreatic tissue. Diabetologia 24, 30–37 (1983). https://doi.org/10.1007/BF00275944
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DOI: https://doi.org/10.1007/BF00275944