In vitro studies on insulin secretion in the genetically obese mouse

Summary Pancreatic insulin content and insulin secretion, from the pancreas of obese mice fed ad lib (ob/ob), obese mice maintained on a restricted diet (ob/ob RD) and lean mice has been studied using incubated pieces of pancreas in vitro and in a perifusion system. The ob/ob mice pancreas contained approximately twice as much insulin as the lean mice pancreas, whereas the ob/ob RD mice had a normal insulin content. Increasing the glucose concentration had a marked and prolonged stimulating effect on insulin secretion in the pancreas of the ob/ob and ob/ob RD mouse, but not in the lean mouse. Leucine stimulated insulin secretion in all three groups of animals both in the absence and presence of glucose in a biphasic manner; in the presence of glucose the insulin secreted from the pancreas of the ob/ob and ob/ob RD mice was abnormally high. Arginine stimulated insulin secretion from the lean mouse pancreas in the absence of glucose, whereas in the obese mouse pancreas stimulation was observed only in the presence of glucose, and the effect increased with increasing glucose concentration. The large amounts of insulin which can be secreted by the pancreas of the ob/ob and ob/ob RD mice under stimulation suggest that an abnormal response of the pancreas to biological stimuli of insulin secretion could be a primary defect in these animals.