Pharmacological modifications of insulin release in vitro from fuel-responsive transplantable insulinomas

The response of insulinoma tissue to glucose, alpha-ketoisocaproate, and the modifiers of insulin release, tolbutamide, isoproterenol, and acetylcholine, was studied. Tumor tissue was transplanted under the kidney capsule of 14 rats, and the tumor-bearing kidneys were perfused in vitro about 8 weeks later. The plasma glucose concentration of these animals was 85.0 +/- 7.0 mg/dl, while the plasma insulin concentration was 13.8 +/- 1.5 ng/ml (normal, 180.5 +/- 7.0 mg/dl and 2.6 +/- 0.5 ng/ml, respectively; n = 26). Glucose (30 mM) evoked a 3- to 5-fold increase in insulin secretion, similar to the increase seen when either 100 micrograms/ml tolbutamide or 0.5 micrograms/ml isoproterenol were added to the perfusion medium containing 5 mM glucose. Propranolol at 50 micrograms/ml, but not at 20 micrograms/ml, inhibited insulin release stimulated by isoproterenol. Acetylcholine (10 or 100 microM) did not stimulate insulin secretion. alpha-Ketoisocaproate caused the highest insulin release of all stimuli studied. Glucagon or somatostatin release was not seen in any of the experiments. These results show that the tumor tissue transplanted under the kidney capsule responds not only to model fuels, but also to the sulfonylurea class of drugs and to adrenergic agents.