Studies on Rats with Islet Beta Cell Tumors Induced by Nicotinamide and Streptozotocin

Summary Islet beta cell adenomata were induced in rats by combined treatment with nicotinamide and streptozotocin. Three weeks after treatment marked alterations in glucose tolerance were noted in animals which later exhibited large beta cell tumors. Eight months after treatment, the rats known to have beta cell tumors on the basis of marked hypoglycemia and later confirmed by autopsy showed variable response to a glucose load. Some tumor-bearing rats showed fast response to glucose load, their blood sugar levels were elevated moderately and returned to normal or below normal levels rapidly; these animals are described as having “fast-acting tumors.” Rats with “slow-acting tumors” responded sluggishly to a glucose load; their blood glucose pattern was similar to that of subdiabetic animals. Animals with beta cell tumors exhibited elevated serum insulin levels 30 min after glucose administration. Insulin biosynthesis by beta cell adenomata was demonstrated by in vitro incorporation of [14C]leucine into proinsulin and insulin. In the small number of tumor samples studied, a stimulatory effect of glucose on insulin biosynthesis was observed. Our grateful thanks to Dr. William E. Dulin, The Upjohn Co., Kalamazoo, Michigan, for the gift of streptozotocin, and to Mr. Steven Koziol of Pharmacia Lab, Piscataway, New Jersey, for Phadebas Insulin Test Kits. The Minnesota Medical Foundation aided this research. This paper is dedicated to the memory of the late Dr. Arnold Lazarow.