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Am J Physiol Regul Integr Comp Physiol 287: R568-R574, 2004. First published May 6, 2004; doi:10.1152/ajpregu.00213.2004
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Amylin receptor blockade stimulates food intake in rats

Roger D. Reidelberger,1,2 Alvin C. Haver,1 Urban Arnelo,3 D. David Smith,2 Courtney S. Schaffert,1 and Johan Permert3

1Department of Veterans Affairs Nebraska Western Iowa Health Care System, Omaha 68105; 2Department of Biomedical Sciences, Creighton University, Omaha, Nebraska 68178; and 3Department of Surgery, Karolinska Institutet at Huddinge University Hospital, S-14186 Stockholm, Sweden

Submitted 30 March 2004 ; accepted in final form 3 May 2004

Amylin is postulated to act as a hormonal signal from the pancreas to the brain to inhibit food intake and regulate energy reserves. Amylin potently reduces food intake, body weight, and adiposity when administered systemically or into the brain. Whether selective blockade of endogenous amylin action increases food intake and adiposity remains to be clearly established. In the present study, the amylin receptor antagonist acetyl-[Asn30, Tyr32] sCT-(8–32) (AC187) was used to assess whether action of endogenous amylin is essential for normal satiation to occur. Non-food-deprived rats received a 3- to 4-h intravenous infusion of AC187 (60–2,000 pmol·kg–1·min–1), either alone or coadministered with a 3-h intravenous infusion of amylin (2.5 or 5 pmol·kg–1·min–1) or a 2-h intragastric infusion of an elemental liquid diet (4 kcal/h). Infusions began just before dark onset. Food intake and meal patterns during the first 4 h of the dark period were determined from continuous computer recordings of changes in food bowl weight. Amylin inhibited food intake by ~50%, and AC187 attenuated this response by ~50%. AC187 dose-dependently stimulated food intake (maximal increases from 76 to 171%), whether administered alone or with an intragastric infusion of liquid diet. Amylin reduced mean meal size and meal frequency, AC187 attenuated these responses, and AC187 administration alone increased mean meal size and meal frequency. These results support the hypothesis that endogenous amylin plays an essential role in reducing meal size and increasing the postmeal interval of satiety.

receptor antagonist; AC187; satiety; islet amyloid polypeptide



Address for reprint requests and other correspondence: R. D. Reidelberger, VA-Nebraska Western Iowa Health Care System, Research Service (151), 4101 Woolworth Ave., Omaha, NE 68105. roger.reidelberger{at}med.va.gov




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