Insulin release from the pancreas in response to glucose appears at the end of gestation in the fetal rat and develops completely in the neonatal period. To determine when this response begins to occur in fetal pancreases transplanted into adult animals, in vitro perfusions were performed in normal and diabetic rats after varying periods of growth. Responsivity to a 300 mg/dl glucose as opposed to a basal medium (50 mg/dl) was not present in the transplanted organ after 3 or 5 wk of growth in normal rats, despite a rise in total insulin content from 88 ± 10 mU to 197 ± 10 mU per two pancreases. Transfer of the pancreases—after 3 wk in the normal—to a diabetic rat for 2 wk resulted in a greater insulin content (343 ± 15 mU) and more insulin being released during perfusion with the basal medium (1863 ± 56 vs. 1374 ± 113 μU/h). Insulin release from these pancreases doubled during perfusion with the high glucose medium rather than with the basal medium. When the transplanted pancreas was left in the normal rats for 5 wk before being transferred to the diabetic animal for 2 wk, the insulin content increased (450 ±10 mU) but there was no response to the glucose challenge during perfusion, despite good function, indicated by a response of all transplanted animals in the diabetic state. We conclude that glucose-induced insulin release will develop in the fetal rat pancreas transplanted into an adult animal after exposure to hyperglycemia, but optimal function requires a period of prior normoglycemia. Careful control of blood glucose with insulin may provide these conditions and will be required when this method is applied to diabetic patients.

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