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Male rats of approximately 200 gm. body weight were injected intravenously with alloxan (40 mg. per kilogram body weight). Blood glucose determinations were carried out at periodic intervals. Plasma samples and acid alcohol extracts of pancreas were assayed by the two antibody method. Five animals were killed at each of the following times: 0, 24, 48, 72 and 96 hrs. The blood glucose concentrations were three times greater than the zero-hour values at each of the latter time periods. In spite of the hyperglycemia at twenty-four hours, there was only a slight decrease in the pancreatic insulin content at this time. Thereafter, the insulin content of pancreatic extracts decreased progressively with time, and at ninety-six hours the insulin concentration was less than 10 per cent of the zero-hour value. The immunoassayable insulin concentration of the plasma did not increase as the pancreatic insulin decreased. These findings suggest that alloxan damaged beta cells did not release their insulin in response to hyperglycemia but that the insulin was destroyed within the beta cell.

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Twenty to thirty-five neonatal rat pancreases (2.5 to 4.5 days postpartum) were minced, dissociated in a collagenasetrypsin-EDTA solution, washed, centrifuged, resuspended in Tyrode's solution, and transplanted intraperitoneally to an alloxan-diabetic recipient. All of eight highly inbred moderate-diabetic rats (mean pretransplant blood sugar level and daily urine glucose excretion = 340 mg./100 ml. and 6.0 gm., respectively), showed a reversal of the diabetes within several days following isotransplantation (blood sugar and daily urine glucose excretion levels dropped to less than 150 mg./100 ml. and 0.1 gm., respectively). Two of seven highly inbred severe-diabetic rats (mean pretransplant blood sugar level and daily urine glucose excretion = 440 mg./100 ml. and 8.0 gm., respectively), recovered from their diabetes about two weeks following isotransplantation. In these highly inbred recipients which recovered from their diabetes, normoglycemia has persisted for more than five months. Control animals receiving liver transplants showed no significant changes in their diabetes. Exploration of the peritoneal cavity, after two months of remission, demonstrated isolated implants in association with the liver, spleen, pancreas, abdominal wall, etc. Yascularized grafts consisted primarily of cords of heavily granulated (aldehyde fuchsin positive) beta cells. Acinar cells were not identified. By contrast, the recipient pancreas showed few identifiable beta cells (characteristic of alloxan diabetes), but these were heavily granulated, presumably because of the controlled diabetic state. In some grafts, removed several days following implantation, mitotic figures were seen in cells containing aldehyde fuchsin positve granules. Similar homotransplants were carried out in thirty-seven partially inbred moderate-diabetic recipients; 46 per cent showed a transitory recovery from their diabetes lasting three to thirteen days. However, the pretransplant diabetes was re-established in one to three weeks and this was attributed to the rejection of the transplant. These studies indicate that dissociated neonatal pancreas forms functional islet implants capable of reversing diabetes in alloxanized rats.