Teleost Fish Islets: A Potential Source of Endocrine Tissue for the Treatment of Diabetes

Abstract

Anatomical separation of pancreatic islets in some teleost fish makes them a useful source of pancreatic endocrine tissue. Islets were harvested from tropical Tilapia fish ( Oreochromis nilotica) and cultured for 24 hr at 37°C. Eight athymic nude mice were rendered diabetic by streptozotocin (STZ) and transplanted under the kidney capsule with fish islets. After transplantation (Tx), nonfasting blood glucose (n-FBG), which was in all recipients >450 mg/dl, decreased to <100 mg/dl. At 4 and 7 weeks post-Tx, the intraperitoneal (ip) glucose tolerance test was performed in the normoglycemic Tx mice and in six normal controls. In controls, K value (percentage of decline in blood glucose/min) was 1.076 ± 0.383 and in Tx mice it was 0.956 ± 0.336 and 0.869 ± 0.483 at 4 and 7 weeks, respectively ( P = n.s.). Nephrectomy raised the n-FBG to pre-Tx levels. On immunohistochemistry, recipient's pancreata showed atrophic islets with no β-cell granules, while the isletbearing kidneys had distinct β-cells under their capsules. Alginate-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/dl for 14 days and subsequent removal of the capsule raised the n-FBG to the pre-Tx level. Finally, it was found that fish islets can be cultured at 37°C for extended periods of time. Even after 22 weeks, well-granulated morphologically intact βcells were seen on transmission 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 bioartificial pancreas.