Experimental diabetes mellitus in a teleost fish. I. Effect of complete isletectomy and subsequent hormonal treatment on metabolism in the goby, Gillichthys mirabilis

Abstract

The anatomical feature of a single pancreatic endocrine (islet) organ devoid of exocrine tissues and separated from other vital organs in the goby, Gillichthys mirabilis, allowed a relatively simple surgical isletectomy to be performed. Isletectomized (Ix) fish were then evaluated to determine whether the lack of islet hormones would cause the development of symptoms of insulin-dependent diabetes mellitus (IDDM) in a teleost fish. Isletectomy resulted in several symptoms typical of untreated IDDM in mammals. Plasma glucose was 3.5-fold higher in Ix animals (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. Isletectomy also resulted in a significant elevation of plasma beta-hydroxybutyrate (from 0.7-0.8 to 1.0 mmol/liter). The severity of the metabolite imbalances was directly correlated with the degree of food consumption in Ix individuals, suggesting a reduced ability to assimilate dietary nutrients. In addition, distension of the abdomen due to increased food intake and a marked swelling of the urinary bladder suggested hyperphagia and polyuria, respectively, in the Ix animals. Insulin replacement therapy over 2 weeks corrected the glycosuria, polyuria, and hyperphagia and resulted in dose-related reductions in plasma glucose and beta-hydroxybutyrate levels. Injection of Ix animals with GH, on the other hand, produced no significant changes in any of the metabolic parameters measured. The establishment of this unique model of IDDM in an ectothermic vertebrate should prove valuable for future comparative studies on the role of insulin and other pancreatic factors in the regulation of metabolic and growth processes.