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This Article Full Text Full Text (PDF) All Versions of this Article: 287/3/R568    most recent 00213.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Reidelberger, R. D. Articles by Permert, J. Search for Related Content PubMed PubMed Citation Articles by Reidelberger, R. D. Articles by Permert, J.

APPETITE, OBESITY, DIGESTION, AND METABOLISM

Amylin receptor blockade stimulates food intake in rats

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

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