A transplantable insulinoma in the rat.

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Abstract
A transplantable insulinoma was developed in inbred albino rats of the NEDH strain. The original tumor, 1 cm in diameter, was removed from the pancreas of a male parabiont 566 days following 1000 rads (10 J/kg) of total body X-irradiation. The time required for implanted fragments to grow to 0.5-1.5 cm in diameter decreased from 5-8 mo. in the 1st generation to 2-5 mo. in the 7th generation. Successful transplantation in male animals followed for 4 or more months after transplantation was significantly greater than in female animals followed for a similar period of time (96 vs. 69%). Light microscopy and EM revealed that the tumors consisted predominantly of well granulated .beta.-cells. Ultrastructural studies also showed small numbers of D-cells. Tumor extracts contained an average of 223 units of immunoreactive insulin and 25.9 .mu.g of immunoreactive somatostatin per gram wet weight of tissue. Tumors produced increasingly profound hypoglycemia within 2-4 mo. following transplantation, with plasma glucose levels frequently falling to 40 mg/100 ml or lower prior to death. Removal of tumors from chronically hypoglycemic animals resulted in transient rebound hyperglycemia with plasma glucose levels above 300 mg/100 ml within the first 24 h and a gradual decline to normal levels of 129 mg/100 ml in 2-4 days. These observations correlated with findings of marked atropy and degranulation of the .beta.-cells in the pancreas of tumor-bearing animals, and with gradual return of normal light microscopic morphology following tumor removal.