Insulin Secretion in Rats with Elevated Levels of Circulating Growth Hormone Due to MtT-W15 Tumor

Abstract

Circulating levels of growth hormone (GH) in Wistar-Furth rats bearing the MtT-W15 tumor are twenty to thirty times higher than normal. The effect of constantly elevated levels of GH on the pancreatic islets was studied. Tumor-bearing rats (TR) and normal controls (C) were pair-fed for seven weeks. In TR, fasting serum levels of GH and insulin were 599 ± 157 ng./ml. and.142 ± 43 μU./ml., respectively, and only 18.2 ± 1.9 ng./ml. and 26.9 ± 7.9 μU./ml., respectively, in the controls. The islets of TR were enlarged with an islet/acinar ratio of 3.38 per cent (C: 0.82 per cent). The extracted pancreatic insulin was 9.84 ± 0.9 mU./mg. (C: 5.36 ± 0.4 mU./mg.). Incubated slices or isolated islets of TR pancreas released greater amounts of insulin when submitted to glucose stimulation. Incorporation of labeled leucine into insulin was increased also in TR. An exaggerated insulin response to a glucose load was found in vivo (peak value at 30 min., TR: 183 dt 42.5 μU./ml; C: 71 ± 17.9 μU/ml.). None of the TR became diabetic, however, and two to six weeks after removal of the tumors serum GH levels had returned to normal (17.2 μg./ml.) as had insulin levels both fasting (19.0 μU/ml.) and following a glucose load (56.4 μU./mg.). Insulin output by incubated pancreas decreased 50 per cent (26 μU./mg.). The islet/acinar ratio returned to normal but the insulin content remained high. These results indicate that in animals exposed to hjgh levels of endogenous GH there is an increased responsiveness of the islets to glueose stimulation.