EXPERIMENTAL DIABETES-MELLITUS IN A TELEOST FISH .1. EFFECT OF COMPLETE ISLETECTOMY AND SUBSEQUENT HORMONAL TREATMENT ON METABOLISM IN THE GOBY, GILLICHTHYS-MIRABILIS

The anatomical feature of a single pancreatic endocrine (islet) organ devoid of exocrine tissues and separated from other vital organs in th e goby, Gillichthys mirabilis, allowed a relatively simple surgical is letectomy to be performed. Isletectomized (Ix) fish were then evaluate d to determine whether the lack of islet hormones would cause the deve lopment of symptoms of insulin-dependent diabetes mellitus (IDDM) in a teleost fish. Isletectomy resulted in several symptoms typical of unt reated IDDM in mammals. Plasma glucose was 3.5-fold higher in Ix anima ls (approximately 23 mmol/liter) than in intact and sham-Ix controls ( 6-7 mmol/liter), while urinary glucose was increased from less than 4 mmol/liter in controls to greater than 40 mmol/liter in Ix animals. Is letectomy also resulted in a significant elevation of plasma beta-hydr oxybutyrate (from 0.7-0.8 to 1.0 mmol/liter). The severity of the meta bolite imbalances was directly correlated with the degree of food cons umption in Ix individuals, suggesting a reduced ability to assimilate dietary nutrients. In addition, distension of the abdomen due to incre ased food intake and a marked swelling of the urinary bladder suggeste d hyperphagia and polyuria, respectively, in the Ix animals. Insulin r eplacement therapy over 2 weeks corrected the glycosuria, polyuria, an d hyperphagia and resulted in dose-related reductions in plasma glucos e and beta-hydroxybutyrate levels. Injection of Ix animals with GH, on the other hand, produced no significant changes in any of the metabol ic parameters measured. The establishment of this unique model of IDDM in an ectothermic vertebrate should prove valuable for future compara tive studies on the role of insulin and other pancreatic factors in th e regulation of metabolic and growth processes.