Insulin secretion in streptozotocin-diabetic rats transplanted with immunoisolated islets

Abstract

Islet transplantation may be optimized by islet immunoisolation to prevent direct contact between the islet graft and the host tissue. In this study, we examined the glycemia and insulin secretion in streptozotocin-diabetic rats transplanted with islets subjected to immunoisolation with Algire diffusion chamber or with microencapsulation. Two days after diabetes induction by streptozotocin (70 mg/kg i.v.), rats were transplanted i.p. with either 1500 or 3000 islets encapsulated in Algire diffusion chambers, or with either 1500 or 3000 microencapsulated islets. Controls were diabetic rats transplanted i.p. with 1500 overnight-cultured islets not subjected to immunoisolation. In these controls, normoglycemia was evident for 3 weeks and a normal plasma insulin response to glucose infusion (10 mg/min) was seen at day 10 after transplantation. It was found that rats transplanted with 1500 microencapsulated islets similarly were normoglycemic for 3 weeks and that the plasma insulin response to glucose infusion at day 10 was normal. Furthermore, rats transplanted with 3000 microencapsulated islets remained normoglycemic for 6 months, and a glucose infusion performed at 6 months in these rats showed a normal acute plasma insulin response, whereas the second phase of insulin secretion was reduced. In contrast, rats transplanted with 1500 islets immunoisolated in Algire chamber remained hyperglycemic, and rats transplanted with 3000 islets within Algire chamber were normoglycemic for only 2 weeks. We conclude that microencapsulation is superior to the use of diffusion chamber as the immunoisolation technique for islets used for transplantation.