Neurotensin receptor 1 (NTSR1) (NTSR1)

Xenin is a 25-amino acid peptide hormone primarily secreted by enteroendocrine K-cells in the gastrointestinal tract, particularly in response to nutrient ingestion. It functions as a key regulator of metabolic homeostasis by stimulating insulin secretion, delaying gastric emptying, and inducing satiety through both central and peripheral mechanisms. These biological actions are largely mediated through the activation of the Neurotensin receptor 1 (NTSR1), although the full range of its effects may involve additional, as-yet-undefined neural and endocrine pathways, including a cholinergic relay that indirectly modulates pancreatic islet function. In metabolic diseases such as type 2 diabetes, the physiological response to xenin is often impaired, making these pathways an attractive target for therapeutic intervention to restore glycemic control. Currently, there are no clinically approved drugs specifically targeting the xenin receptor, but several experimental agents are in preclinical development. These include stable xenin-25 analogs, bioactive fragments like xenin-8, and multi-agonist hybrid peptides that combine xenin with other gut hormones like glucose-dependent insulinotropic polypeptide (GIP). These compounds aim to leverage the synergistic effects of xenin on insulinotropic signaling and appetite regulation to treat obesity and diabetes. However, challenges such as the rapid proteolytic degradation of native xenin and the complexity of its indirect signaling mechanisms remain significant hurdles in drug development.

Other names

Xenin receptorXenin-25 receptorNTR1NT-R-1Xenin-responsive pathways

Agonism of the Neurotensin receptor 1 (NTSR1) to trigger neural and endocrine signaling pathways that regulate metabolism, including the potentiation of glucose-dependent insulinotropic polypeptide (GIP) action.