Diabetogenic role of insulin's counterregulatory hormones in the isletectomized, diabetic goby.

In an experimental model of insulin-dependent diabetes mellitus (IDDM) in the teleost fish, the goby Gillichthys mirabilis, an isletectomy procedure completely removes the pancreatic endocrine tissue without affecting the exocrine acini or other essential tissues. Interestingly, isletectomized (Ix) gobies do not exhibit a significant hyperglycemia until 10-15 d after this procedure, suggesting a lack of initial diabetogenic actions of a pancreatic factor(s). Administering exogenous glucagon in otherwise nonsymptomatic 7-d Ix gobies, however, induces a hyperglycemic state comparable to that in severely diabetic rats or gobies (after 20 d post-Ix). The spontaneously arising hyperglycemia observed between 10 and 15d post-Ix, on the other hand, is significantly correlated with increasing serum cortisol concentrations, with both exhibiting sustained elevated levels (approx 23 mmol/L and >100 ng/mL, respectively) at 20- and 25-d post-Ix. Exogenous cortisol treatment also significantly induced hyperglycemia in nonsymptomatic, 7-d Ix gobies. By contrast, growth hormone (GH) had no detectable diabetogenic effect in 7-d Ix gobies. Serum levels of ammonia, the principal nitrogenous waste in this species, were not affected by glucagon treatment but were reduced slightly by GH treatment (30% reduction; p < 0.05). Cortisol treatment, on the other hand, increased ammonia levels twofold, suggesting that the glucocorticoid induces a negative nitrogen balance. These results indicate that the counterregulatory hormones--glucagon and cortisol--are effective diabetogenic factors in the Ix goby, capable of driving metabolic imbalance in this model of IDDM.