Glucose homeostasis in the teleost fish tilapia: Insights from Brockmann body xenotransplantation studies

Certain teleost fish have large anatomically discrete islet organs called B rockmann bodies (BBs), When transplanted into streptozotocin diabetic athym ic nude mice, tilapia BBs provide long-term normoglycemia. This has afforde d us the opportunity to examine tilapia islet in vivo function in a non-pis cine environment and compare this with in vivo function in the donor specie s. As expected, fasting and non-fasting glycemic levels in long-term murine recipients of tilapia BBs were analogous to corresponding values in donor tilapia, but, surprisingly, tilapia BE grafts provided mammalian-like gluco se tolerance profiles. Teleost fish, in general, are severely glucose intol erant. When glucose tolerance tests were performed in tilapia, the mean glu cose disappearance rates were very low; however, diabetic nude mice bearing long-term tilapia BE grafts were extremely glucose responsive. This sugges ted a severe or absolute peripheral resistance to the glucostatic effects o f insulin. Using Western blotting with polyclonal antibodies and then confi rmed by Northern analysis, tilapia peripheral tissues appear to be devoid o f GLUT-4 the insulin-sensitive glucose transporter responsible for the hypo glycemic effect of insulin in mammals, but not GLUT-1, the insulin independ ent glucose transporter. This may explain why tilapia, and possibly other t eleost fish, are severely glucose intolerant after pharmacologic glucose-lo ading. Because tilapia do not tend to consume large quantities of glucose i n the wild, it is not surprising that they have evolved without a mechanism to move glucose rapidly from the bloodstream into muscle and fat. Neverthe less, insulin still appears to play an important role in maintaining normog lycemia in tilapia; however, this is mostly Likely a result of its effect o n glucose uptake in the liver. We also present comparative data on tilapia beta cell function, quantification of islet cell numbers and types, islet p roducts, insulin gene structure and expression, and beta cell sensitivity t o the diabetogenic drug streptozotocin.