Serially Transplantable Chemically Induced Rat Islet Cell Tumor*

Abstract

A serially transplantable, chemically induced pancreatic islet cell tumor was developed in Lewis rats. The original tumor was induced by the administration of streptozotocin and nicotinamide. It was subsequently maintained by ip or sc transplantation of tissue fragments into recipient animals. Tumors generally grew to 0.5--2.0 cm in diameter within 3--4 months of transplantation. They were well encapsulated, without gross evidence of metastasis. Peroxidase immunocytochemical staining revealed a predominance of insulin-positive cells. Somatostatin-positive cells were also present and varied widely in numbers between different tumors. In addition, small numbers of glucagon-positive cells were observed in all of the tumors. On electron microscopy, cells containing secretory granules, indistinguishable from nonneoplastic beta-cells, were most abundant. Other granulated cells were also observed, but the granule morphology was not identical to that of any of the other classically described islet cell types. Tumor extracts contained an average of 3260 micrograms insulin, 22.6 micrograms somatostatin, and 0.84 micrograms glucagon per g wet wt of tissue. Tumors caused marked, progressive hypoglycemia in recipients, with plasma glucose levels frequently falling below 30 mg/dl before death. Furthermore, the recipients' islets were markedly reduced in size due to a decreased beta-cell volume.

Effects of transplantation and resection of a radiation-induced rat insulinoma on glucose homeostasis and the endocrine pancreas

“…Attention has recently been given to the induction of serially transplantable insulinomas in animals, which provide useful models to assist elucidation of the underlying cellular defects and the metabolic effects of insulinomas on the regulation of glucose homeostasis. Transplantable islet cell tumours have been established from single pancreatic tumours in hamsters and rats which have arisen either spontaneously, after BK virus innoculation, streptozotocin-nicotinamide injection or X-ray irradiation (Grillo et al, 1967;Hirayama et al, 1979;Chick et al, 1977Chick et al, , 1980. The transplantable NEDH rat insulinoma, developed in the irradiated partner of a pair of parabiont NEDH rats (Chick et al, 1977), offers the advantage of high insulin content and rapid growth rate, resulting consistently in the production of a localised, highly vascularised encapsulated tumour at the subscapular implantation site.…”

<b>ACUTE AND LONG-TERM EFFECTS OF GLUCOSE ON THE FUNCTION OF TRANSPLANTABLE RAT INSULINOMA CELLS MAINTAINED IN TISSUE </b><b>CULTURE </b>

“…These have been produced in the rat by X-ray irradiation or streptozotocin-nicotinamide injection (3,4), in the hamster by BK virus innoculation (15), and in the mouse by transfer into fertilised eggs of recombinant genes (12). Research conducted using these insulinomas has focused on two questions, namely what can these tumours tell us about human insulinomas, and secondly what might be learnt about pancreatic B-cell function by exploiting the availability of large amounts of insulinoma tissue.…”

Defective Diurnal Changes of Food Intake, Plasma Glucose and Insulin in Rats with a Transplantable Islet Cell Tumour

“…Serially transplantable tumours have arisen spontaneously in the hamster or fol- lowing inoculation with BK virus [15,16], while a combination of streptozotocin with nicotinamide or X-ray irradiation have been successfully employed in rats [11,17]. The present study has utilised a subline of the transplantable islet cell tumour produced by X-ray irradiation of one of a pair of para biont inbred NEDH rats [11], Compared with other islet cell tumours, this tumour offers the advantage of high insulin content, being composed almost entirely of well gran ulated B cells, with only small numbers of somatostatin and pancreatic polypeptidecontaining cells [11,18].…”