Effects of acute and chronic infusion of islet amyloid polypeptide on food intake in rats

Background: Islet amyloid polypeptide (IAPP), also called amylin, is a hormonal peptide produced by the islet β-cells of the pancreas. Because the peptide is co-stored and co-released with insulin, attention has been focused on IAPP's ability to interfere with glucose metabolism However, IAPP also has other effects, such as a reduction of food intake. Methods: In this study we investigated the dose-response effect of acute systemic administration of rat and human IAPP on food intake, and the cumulative effect of chronically increased circulating IAPP concentrations on food intake and body weight in the rat. Results: All doses of rat IAPP investigated acutely inhibited food intake. The lowest 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. Chronic administration of rat IAPP via an osmotic minipump during a 6-day period caused prolonged inhibitory effects on food intake and reduced body 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 throughout the last 3 days of study (LAPP, 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 group and +10.9 ± 4.8 for the central group (p < 0.01). Conclusions: These findings show that chronic increase of circulating IAPP levels can cause a marked reduction in both food intake and body weight and, together with the reduced food intake seen after acute administration of the peptide, indicates the possibility of IAPP functioning as a satiety factor.