Experimental diabetes mellitus in a teleost fish. II. 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 controlled in mammals, results in growth retardation. To determine whether the same relationship exists in an ectothermic vertebrate, IDDM-like symptoms were induced in a teleost fish, the goby Gillichthys mirabilis, by surgical removal of its pancreatic endocrine (islet) organ. Isletectomized (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 35SO4 incorporation in vitro, consistent with changes that occur in mammals with IDDM. Injections of bovine insulin into the Ix fish restored body growth parameters to control levels and stimulated cartilage 35SO4 incorporation in a dose-related manner. In contrast to mammals with IDDM, which are resistant to GH action, injection of teleost GH stimulated cartilage 35SO4 incorporation 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 responsive to recombinant bovine IGF-I, exhibiting a dose-dependent stimulation of 35SO4 incorporation. As far as we are aware, these results represent the first demonstration of diabetic growth inhibition in an ectothermic 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 promotion of anabolic processes.
Department of Integrative Biology, University of California, Berkeley 94720.
K M
KM
Kelley
E S
ES
Gray
K
K
Siharath
C S
CS
Nicoll
H A
HA
Bern
D000818:Animals; D002356:Cartilage / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000601:surgery; D005399:Fishes / Q000502:physiology*; D006130:Growth Disorders / Q000209:etiology / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism / Q000502:physiology; D006728:Hormones / Q000502:physiology*; D007328:Insulin / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D007515:Islets of Langerhans / Q000601:surgery; D008099:Liver / Q000378:metabolism*; D011986:Receptors, Somatotropin / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism
D006728:Hormones; D007328:Insulin; D011986:Receptors, Somatotropin; D013431:Sulfates; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone