Insulin Storage and Release in Rats Bearing Growth Hormone Secreting Tumors Free

The effects of chronic hypersomatotropism on pancreatic islet function were studied in rats bearing the growth hormone secreting tumor MtTW15. These rats did not become hyperglycemic and minimally hyperinsulinemic in the fed state following prolonged massive elevations of serum growth hormone. Islets from tumor-bearing rats were grossly larger and beta cells more granulated than in control rats by light microscopy. Electron microscopy confirmed the increase in cell cytoplasm and increased number of beta granules per cell. Isolated islet preparations from tumor-bearing rats contained four times the insulin found in control rats. Fed control and tumor-bearing rats had comparable serum glucose and immunoreactive insulin concentrations after glucose intragastrically and tolbutamide intravenously. After a forty-eight-hour fast the tumor-bearing rats had higher serum immunoreactive insulin than controls and their insulin levels were higher after glucose and tolbutamide than controls. Some of the tumor-bearing rats became hypoglycemic during the forty-eight-hour fast. The increased stored insulin in the tumor-bearing rats was mobilized by a combination of the individually potent insulinogenie stimuli theophylline and glucagon.