Insulin Content of Fetal Mouse Pancreas in Organ Culture and After Transplantation

Abstract

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.