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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.

Islet amyloid polypeptide (IAPP, or amylin) is produced in pancreatic β-cells. The intraislet significance of IAPP is still uncertain. In the present study, paracrine effects of endogenous IAPP and somatostatin were investigated in isolated rat pancreatic islets. The intraislet IAPP activity was inhibited with an IAPP antiserum or a specific antagonist [IAPP-(8—37)]. Somatostatin activity was inhibited by immunoneutralization. Basal insulin and glucagon secretion were not affected by the somatostatin and/or IAPP blockade. Arginine-stimulated insulin and glucagon secretion were dose dependently increased by IAPP antiserum, IAPP-(8—37), and somatostatin antiserum, respectively. Arginine-stimulated somatostatin secretion was dose dependently potentiated by IAPP antiserum. Insulin secretion induced by 16.7 mM glucose was enhanced by IAPP antiserum and IAPP-(8—37), respectively. A combination of somatostatin antiserum with IAPP antiserum or IAPP-(8—37) further enhanced the arginine-stimulated insulin and glucagon secretion compared with effects when the blocking reagents were used individually. These results indicate that endogenously produced IAPP tonally inhibits stimulated insulin, glucagon, and somatostatin secretion. Furthermore, the paracrine effects of IAPP and somatostatin are additive.

Our objective was to study whether islet amyloid polypeptide (IAPP) produces satiety by an endocrine mechanism. We used a rat model to determine whether postprandial plasma levels of IAPP are comparable to those required to inhibit feeding when IAPP is administered by continuous intravenous infusion. Food intake in rats with aortic catheters increased plasma IAPP levels from a fasting level of 10.8 ± 0.5 pM to a peak level of 19.0 ± 1.0 pM at 2.2 ± 0.5 h. In rats with jugular vein and aortic catheters, the threshold intravenous dose for IAPP suppression of feeding was between 1 and 3 pmol ⋅ kg−1 ⋅ min−1. The 3 pmol ⋅ kg−1 ⋅ min−1dose decreased 4-h intake by ∼25% by decreasing meal frequency rather than meal size. This dose increased plasma IAPP by ∼24 pM. These results suggest that postprandial plasma levels of IAPP are not quite sufficient to independently produce satiety.