HYPERSECRETION OF AMYLIN FROM THE PERFUSED PANCREAS OF GENETICALLY-OBESE (FA/FA) RATS AND ITS ALTERATION WITH AGING

To evaluate the relationship between the development of obesity and the hypersecretion of amylin by the pancreas, we examined the effects of 16.7 mmol/L glucose and 10 mmol/L arginine on the secretion of amylin and insulin by isolated perfused pancreata from genetically obese ( fa fa) and lean (Fa/?) Zucker rats at 9, 18, and 54 weeks of age. Concentrations of amylin and insulin in the effluent were measured by radioimmunoassay (RIA). Pancreata of obese rats secreted greater amounts of amylin in response to 16.7 mmol/L glucose and 10 mmol/L arginine than did those of lean rats at all ages. The hypersecretion of amylin by obese rats was particularly marked at 18 weeks of age, when they showed the most rapid increase in body fat mass. This hypersecretion became obscure at 54 weeks of age, when obese rats showed the maximum body weight. The pattern of amylin release resembled that of insulin in all groups. However, the relative amount of amylin to insulin secreted following stimulation with 16.7 mmol/L glucose and 10 mmol/L arginine in obese rats exceeded that in lean rats at all ages. Differences in the secreted amylin to insulin molar ratios between obese and lean rats were significant when pancreata were stimulated with glucose at 18 weeks (obese, 1.23% ± 0.05%; lean, 0.99% ± 0.04%; P < .01), glucose at 54 weeks (P < .01), and arginine at 54 weeks (P < .05). These data suggest that (1) hypersecretion of amylin by pancreata of genetically obese ( fa fa) rats may be linked to the development of obesity; and (2) obesity may increase the production ratio of amylin to insulin by the pancreatic β cell. © 1993.