Quantitative aspects of the metabolic response to pancreatic islet transplantation in rats with severe ketotic diabetes.

Injection of 100-140 mg/Kg of streptozotocin produced severe, ketotic diabetes in 12 pairs of adult rats. Transplantation of intact islets of Langerhans from syngeneic adult donors into a muscle pocket or a pouch created from pancreatic tissue of one animal from each pair eliminated ketonemia in the immediate postoperative period, while ketonemia persisted in the sham-operated controls. Mean survival of transplanted animals was 145 days, versus 70 days for controls. Mean body weight increased and blood sugar decreased in transplanted animals compared with controls; the differences were greatest in those animals which received the largest number of islets per unit body weight. In one animal, all metabolic indices returned to normal for a period of 8 wk following transplantation of 650 islets. After gaining to 300% of initial body weight, diabetes reappeared in this transplanted animal and was again reversed by a second transplantation. The metabolic data indicate that: (1) islet tissue from adult donors survives and functions in severely diabetic, ketotic hosts; and (2) metabolic response to transplantation is a function of the ratio of islet tissue to body mass, a minimum ratio of about 2-3 islets/gm body weight being required to maintain normal homeostasis.