CHRONIC INFUSION OF ISLET AMYLOID POLYPEPTIDE CAUSES ANOREXIA IN RATS

Islet amyloid polypeptide (IAPP) is a hormonal peptide that at high do ses has been shown to reduce food intake. In the present study, the do se-response effects of subcutaneous infusion of IAPP (0, 2, 7, and 25 pmol . kg(-1). min(-1)) for 8 days on food intake and meal patterns in rats were investigated. At the end of the experiment, plasma was obta ined and levels of IAPP were measured by radioimmunoassay. IAPP dose-d ependently and transiently inhibited food intake. The minimal effectiv e dose (2 pmol . kg(-1). min(-1)) caused a small but significant (up t o 14%, P < 0.01) inhibition of food intake that lasted 5 days. The hig hest dose administered (25 pmol . kg(-1). min(-1)) had the greatest ef fect (up to 44%, P < 0.001), which lasted throughout the 8-day period. Reductions in feeding during light and dark phases occurred through a decrease in number of meals consumed rather than meal size or meal du ration. IAPP also decreased body weight gain and water intake dose dep endently. IAPP infusion of 2, 7, and 25 pmol . kg(-1). min(-1) increas ed plasma IAPP concentrations from a basal level of 10.3 +/- 0.7 pM to 35.1 +/- 5.4, 78.1 +/- 11.2, and 236.6 +/- 23.6 pM, respectively, val ues that are likely to be close to physiological and within the pathop hysiological ranges. Thus IAPP may play an important physiological or pathophysiological role in control of food intake.