Once thought to be a unique capability of the Langerhans Islands in the
pancreas of mammals, insulin production is now recognized as an
evolutionarily ancient function going back to prokaryotes, ubiquitously
present in unicellular eukaryotes, fungi, worm, Drosophila and of course
human. While the functionality of the signaling pathway has been
experimentally demonstrated in some of these organisms, it has not yet
been exploited for pharmacological applications. To enable such
applications, we need to understand the extent to which the structure
and function of the insulin-insulin receptor system is conserved. To
this end, we analyzed the insulin signaling pathway in corals through
remote homology detection and modeling. By docking known insulin
receptor ligands to a coral homology structure, we locate ligand binding
pockets and demonstrate their conservation suggesting that it may be
possible to exploit the structural conservation for pharmacological
applications in non-model organisms. We also identified the coral
homologues of the over 100 signaling proteins involved in insulin and
its related signaling pathways, demonstrating their wide-spread
conservation. Notable exceptions are glucagon and somatostatin. It is
tempting to speculate that under high light conditions, when the algae
synthetize excess sugars, the cnidarian host may experience insulin
resistance, and that the cnidarian microbiome may be involved in
manipulating the insulin signaling system.