EFFECTS OF ACUTE AND CHRONIC INFUSION OF ISLET AMYLOID POLYPEPTIDE ONFOOD-INTAKE IN RATS

Background: Islet amyloid polypeptide (IAPP), also called amylin, is a hormonal peptide produced by the islet B-cells of the pancreas. Becau se the peptide is co-stored and co-released with insulin, attention ha s been focused on IAPP's ability to interfere with glucose metabolism. However, IAPP also has other effects, such as a reduction of food int ake. Methods: In this study we investigated the dose-response effect o f acute systemic administration of rat and human IAPP on food intake, and the cumulative effect of chronically increased circulating IAPP co ncentrations on food intake and body weight in the rat. Results: All d oses of rat IAPP investigated acutely inhibited food intake. The lowes t infusion rate of 8 pmol/kg/min caused an 28% inhibition of the food intake at 2 h (p < 0.05). No effect of human IAPP was observed. Chroni c administration of rat IAPP via an osmotic minipump during a 6-day pe riod caused prolonged inhibitory effects on food intake and reduced bo dy weight. During the first 3 days of infusion the food intake of the IAPP group was only 44% of the food intake of the control group (p < 0 .001). The body weight of the IAPP group had fallen 18.6 +/- 2.7 g by day 3, in contrast to a small increase in the control group (4.0 +/- 3 .1 g; p < 0.001). The reduction in food intake was sustained throughou t the last 3 days of study (IAPP, 16.7 +/- 1.1 g/day; control, 20.6 +/ - 1.5; p < 0.05). Similarly, the body weight still differed at the end of day 6 and, compared with day 0, was -8.7 +/- 3.7 g for the IAPP gr oup and +10.9 +/- 4.8 for the control group (p < 0.01). Conclusions: T hese findings show that chronic increase of circulating IAPP levels ca n cause a marked reduction in both food intake and body weight and, to gether with the reduced food intake seen after acute administration of the peptide, indicates the possibility of IAPP functioning as a satie ty factor.