Amylin receptor blockade stimulates food intake in rats.
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-[Asn(30), Tyr(32)] 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 approximately 50%, and AC187 attenuated this response by approximately 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.
Reidelberger
Roger D
RD
Department of Veterans Affairs Nebraska Western Iowa Health Care System, Research Service (151), 4101 Woolworth Ave., Omaha, NE 68105, USA. roger.reidelberger@med.va.gov
Haver
Alvin C
AC
Arnelo
Urban
U
Smith
D David
DD
Schaffert
Courtney S
CS
Permert
Johan
J
D000682:Amyloid / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000503:physiopathology; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D004750:Enteral Nutrition; D005526:Food, Formulated; D007275:Injections, Intravenous; D007441:Intubation, Gastrointestinal; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors / Q000502:physiology*
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; D010455:Peptides; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide; C087166:AC 187