Amylin is secreted by pancreatic beta-cells and is believed to be a physiological signal of satiation.
Amylin's effect on eating has been shown to be mediated via a direct action at the area postrema (AP) via
amylin receptors that are heterodimers of the
calcitonin receptor core
protein with a
receptor activity modifying protein. Peripheral
amylin leads to accumulation of cyclic
guanosine monophosphate, phosphorylated
extracellular-signal regulated kinase 1/2 and
c-Fos protein in AP neurons. The particular
amylin-activated AP neurons mediating its anorexigenic action seem to be noradrenergic. The central pathways mediating
amylin's effects have been characterized by lesioning and tracing studies, identifying important connections from the AP to the nucleus of the solitary tract and lateral parabrachial nucleus.
Amylin was shown to interact, probably at the brainstem, with other signals involved in the short term control of food intake, namely
cholecystokinin,
glucagon-like peptide 1 and
peptide YY.
Amylin also interacts with the adiposity signal
leptin; this interaction, which is thought to involve the hypothalamus, may have important implications for the development of new and improved hormonal
obesity treatments. In conclusion,
amylin actions on food intake seem to reside primarily within the brainstem, and the associated mechanisms are starting to be unraveled. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.