ALPHA-CELL AND BETA-CELL FUNCTION IN OBESE ZUCKER (FA FA) RATS - A STUDY WITH THE ISOLATED-PERFUSED PANCREAS/

1. The effects of various stimuli, including changes in glucose concen tration, arginine, tyramine and noradrenaline, on insulin and glucagon secretion were investigated using isolated perfused pancreata of obes e and lean male Zucker rats at 12 months of age. 2. In Zucker fatty ra ts, the insulin secretion rate was significantly (P < 0.01) higher tha n that of lean rats at all glucose concentrations tested (8.3, 16.7 an d 1.4 mmol/l). However, the integrated insulin secretory response to r aising the glucose concentration from 8.3 to 16.7 mmol/l was almost ab sent in these rats. The glucagon secretion rates were significantly lo wer at 8.3 and 14 mmol/l glucose (P < 0.001 for both), and in response s to 10 mu g/ml tyramine and 0.1 mu mol/l noradrenaline (P < 0.05 for both), in Zucker fatty rats. Integrated insulin and glucagon responses to 10 mmol/l arginine were identical in the two groups. 3. Histopatho logical and immunochemical studies revealed hyperplasia of beta-cells and scattered alpha-cells in the enlarged islets of Zucker fatty rats. 4. These results suggest that, in Zucker fatty rats, the decreased gl ucagon secretion in the isolated perfused pancreas is attributable to changes in the environment of alpha-cells and/or the inhibitory effect s of hypersecreted insulin.