Organ-cultured fetal mouse pancreas was transplanted into syngeneic diabetic mice and the insulin content of the graft measured. Insulin content of each 17-day-old uncultured fetal mouse pancreas was 90 ± 10 ng, rising to 457 ± 123 ng after 16 days in organ culture (P < 0.001); however, after 35 days in vitro, it decreased to 108 ± 59 ng. Diabetes was induced in mice with streptozotocin (STZ), and 3 wk later each animal was grafted under the kidney capsule with one syngeneic fetal pancreas cultured for 16 days. Total insulin content of fetal pancreata increased from 457 ± 123 ng on the day of transplantation to peak at 12,125 ± 3679 ng by 9 wk after grafting (P < 0.001), at which time insulin content of grafts was comparable to that extracted from normal adult mouse pancreas (8917 ± 436 ng). Random blood glucose in mice following STZ was 15.7 ± 0.9 mmol/L and declined to normal levels (5.6 ± 0.5 mmol/L) 6 wk after transplantation. Insulin content of the pancreas after STZ injection decreased from 8917 ± 436 ng to 906 ± 410 ng at 15 wk (P < 0.001) in diabetic mice that were not islet grafted. However, pancreatic insulin content of grafted mice was significantly greater than in ungrafted mice 15 wk after STZ (3168 ± 532 ng versus 906 ± 410 ng, P 0.01), which suggests that islet transplantation protects residual pancreatic function. It is concluded that fetal islets have a large capacity to produce and accumulate insulin in vitro and in vivo, and each grafted fetal pancreas may attain an insulin content equivalent to that of a normal adult pancreas. The potential of fetal islets to accumulate large insulin reserves may make possible the use of tissue from one donor to treat multiple recipients.

This content is only available via PDF.