Numerous studies have established the pancreatic B-cell
hormone amylin as an important
anorectic peptide affecting meal-ending satiety. In the present study, we investigated the effect of a chronic infusion of the
amylin antagonist
AC 187 on food intake. The studies were performed using obese Zucker fa/fa rats, which are hyperamylinemic but have a defective
leptin and
insulin signaling system. A chronic
intraperitoneal infusion of the
amylin antagonist
AC 187 (10 microg/kg/h) significantly increased dark phase and total food intake in Zucker but not in lean control rats. During the 8-day infusion experiment,
AC 187 had no clear effect on
body weight gain in either group. After acute administration,
amylin and its agonist
salmon calcitonin (sCT) equally reduced food intake in Zucker and lean control rats while
cholecystokinin's (CCK)
anorectic effect was weaker in the Zucker rats. We provide evidence for
amylin being a potential long-term regulator of food intake because
AC 187 increased food intake in obese fa/fa rats but not in lean control animals, which have low baseline
amylin levels.
Amylin may play some role as lipostatic feedback signal similar to
leptin and
insulin at least when the
leptin and
insulin feedback signaling systems are deficient. Despite basal hyperamylinemia in the Zucker rats, they do not seem to be less sensitive to the
anorectic effects of
amylin or its agonist sCT than respective controls. This contrasts with CCK whose
anorectic action is reduced in Zucker rats when compared with lean controls.