STUDIES OF THE FUNCTIONAL AND MORPHOLOGIC STATUS OF ISLETS MAINTAINED AT 24-C FOR 4 WEEKS INVITRO

  • 1 January 1979
    • journal article
    • research article
    • Vol. 97  (3) , 489-+
Abstract
The immune barrier represents a major deterrent for the application of islet transplantation to the therapy of human diabetics. Isolated rat islets were maintained in vitro at 24.degree. C for 1-4 wk in tissue culture medium containing D-glucose (1.5 mg/ml). The rate of insulin release at 24.degree. C remained stable for 3 wk (2.2 .mu.U/[unit]/islet per h) and decreased to 1.2 .mu.U/islet per h during the 4th wk. Increasing the temperature from 24.degree. to 37.degree. C at the end of 1, 2, 3 or 4 wk produced a 5-7-fold increase in the rate of insulin release in the presence of glucose (1.5 mg/ml). This rate of secretion was comparable to control islets maintained at 37.degree. C for 1-4 wk. Light microscopic and EM studies revealed minimal central necrosis of large islets maintained at 24.degree. C for 3 wk. In contrast, extensive central necrosis was present in large islets maintained at 37.degree. C for only 1 wk. Degranulation of .beta. cells occurred at 24.degree. C with almost complete degranulation at 28 days. Regranulation occurred when the temperature was increased to 37.degree. C. Isolated islets maintained at 24.degree. C evidently remain functionally and morphologically intact for 4 wk. Maintenance of islets at 24.degree. C for 1 wk in conjunction with a single injection of antilymphocyte serum will produce marked prolongation of survival of islet allografts. The finding that isolated islets will survive for prolonged periods of time at 24.degree. C should be of importance to future studies on islet transplantation, immune rejection and investigations on hormonal release from islets maintained under these conditions.