EXPERIMENTAL DIABETES-MELLITUS IN A TELEOST FISH .2. ROLES OF INSULIN, GROWTH-HORMONE (GH), INSULIN-LIKE GROWTH FACTOR-I, AND HEPATIC GH RECEPTORS IN DIABETIC GROWTH-INHIBITION IN THE GOBY, GILLICHTHYS-MIRABILIS

Insulin-dependent diabetes mellitus (IDDM), when untreated or poorly c ontrolled in mammals, results in growth retardation. To determine whet her the same relationship exists in an ectothermic vertebrate, IDDM-li ke symptoms were induced in a teleost fish, the goby Gillichthys mirab ilis, by surgical removal of its pancreatic endocrine (islet) organ. I sletectomized (Ix) gobies lost body weight, their skeletal growth was retarded, as measured by changes in body length, and they exhibited a 50% reduction in cartilage (SO4)-S-35 incorporation in vitro, consiste nt with changes that occur in mammals with IDDM. Injections of bovine insulin into the Ix fish restored body growth parameters to control le vels and stimulated cartilage (SO4)-S-35 incorporation in a dose-relat ed manner. In contrast to mammals with IDDM, which are resistant to GH action, injection of teleost GH stimulated cartilage (SO4)-S-35 incor poration in the Ix fish. Furthermore, whereas cartilage from rats with IDDM is resistant to stimulation by insulin-like growth factor-I (IGF -I) in vitro, cartilage explants from the Ix fish were highly responsi ve to recombinant bovine IGF-I, exhibiting a dose-dependent stimulatio n of (SO4)-S-35 incorporation. As far as we are aware, these results r epresent the first demonstration of diabetic growth inhibition in an e ctothermic vertebrate. This inhibition is similar to that which occurs in mammals with IDDM in some respects, but is different in others, as the diabetic fish did not develop resistance to growth stimulation by either GH or IGF-I. While these results support a role for insulin in maintaining the GH-IGF-I-growth axis in this ectothermic vertebrate, there may be important differences in the role of insulin in the promo tion of anabolic processes.