Apelin Pancreas Signaling Pathway

The apelin gene is X-linked and is synthesized as a 77 amino acid pre-pro-peptide that is cleaved post-translationally to generate several active forms whose lengths range from 36 to 12 amino acids. These isoforms possess similar functions but display different tissue distribution, potency and receptor binding affinity. Apelin acts as a ligand for the APJ receptor (angiotensin II receptor like-1, AT-1), which is coupled to pertussis toxin (PTX)-sensitive G proteins. The apelin/APJ system plays important and various roles in the physiology and pathophysiology of many organs, including regulation of blood pressure, angiogenesis, cardiac contractility, metabolic balance, cell proliferation and apoptosis. It is noteworthy that the APJ receptor is also activated by APELA, a distinct peptide hormone with significant effects on cardiac development.
Apelin is an adipocytokine secreted by adipocytes that tends to counteract diabetes mellitus and diabetic complications. It is also generated by the pancreas itself in response to injury, and reduces the damaging inflammatory responses of pancreatitis.
The main effect of apelin on pancreas is inhibition of insulin secretion through AMPK activation and downregulation of cAMP. Long-term apelin treatment significantly ameliorates diabetes-induced reduction in pancreatic islet mass by decreasing endoplasmic reticulum stress through upregulation of ERN1-JNK/EIF2AK3-DDIT3 signaling.