TELEOST FISH ISLETS - A POTENTIAL SOURCE OF ENDOCRINE TISSUE FOR THE TREATMENT OF DIABETES

Anatomical separation of pancreatic islets in some teleost fish makes them a useful source of pancreatic endocrine tissue. Islets were harve sted from tropical Tilapia fish (Oreochromis nilotica) and cultured fa r 24 hr at 37 degrees C. Eight athymic nude mice were rendered diabeti c by streptozotocin (STZ) and transplanted under the kidney capsule wi th fish islets. After transplantation (Tx), nonfasting blood glucose ( n-FBG), which was in all recipients >450 mg/dl, decreased to <100 mg/d l. At 4 and 7 weeks post-Tx, the intraperitoneal (ip) glucase toleranc e test was performed in the normoglycemic Tx mice and in six normal co ntrols. In controls, K value (percentage of decline in blood glucose/m in) was 1.076 +/- 0.383 and in Tx mice it was 0.956 +/- 0.336 and 0.86 9 +/- 0.483 at 4 and 7 weeks, respectively (P = n.s.). Nephrectomy rai sed the n-FBG to pre-Tx levels. On immunohistochemistry, recipient's p ancreata showed atrophic islets with no beta-cell granules, while the islet-bearing kidneys had distinct beta-cells under their capsules. Al ginate-embedded fish islets were encapsulated in permselective (25-kDa ) cellulose membranes and implanted ip in six STZ-diabetic nude mice. On the following day, all recipients became normoglycemic and their n- FBG remained normal for 7 days. In one animal, the n-FBG was <200 mg/d l for 14 days and subsequent removal of the capsule raised the n-FBG t o the pre-Tx level. Finally, it was found that fish islets can be cult ured at 37 degrees C for extended periods of time. Even after 22 weeks , well-granulated morphologically intact beta-cells were seen on trans mission electron microscopy. In conclusion, we have demonstrated that fish pancreatic islets can be maintained in culture for exceptionally prolonged periods of time, that they can successfully be transplanted in mammals, and that there is a potential for their use in the bioarti ficial pancreas. (C) 1995 Academic Press,Inc.