Islet neogenesis-associated protein receptor (INGAP-R)

The Islet neogenesis-associated protein receptor (INGAP-R) is a cell surface protein that plays a pivotal role in pancreatic regeneration and glucose metabolism (Rosenberg et al., 2004, PubMed: 15190075). It serves as the primary binding site for Islet Neogenesis-Associated Protein (INGAP), a member of the Reg (Regenerating) protein family, specifically the human ortholog Reg3A (Taylor-Fishwick et al., 2003, PubMed: 12644616). Upon activation, the receptor initiates signaling cascades, including the MAPK/ERK and PI3K/Akt pathways, which stimulate the differentiation of pancreatic ductal cells into new beta cells and promote the proliferation of existing ones (Arribas et al., 2006, PubMed: 17065234). This process, termed islet neogenesis, is a key mechanism for increasing functional beta-cell mass (Rosenberg et al., 2004). In therapeutic development, the receptor is targeted by the synthetic peptide INGAP-P (Exsulin) to treat Type 1 and Type 2 diabetes by restoring endogenous insulin production (ClinicalTrials.gov, NCT00067418). Although some research identifies Exostosin-like 3 (EXTL3) as the molecular identity of the Reg/INGAP receptor, it remains widely characterized in clinical pharmacology by its association with INGAP-mediated islet growth (Taylor-Fishwick et al., 2003). The receptor is primarily expressed in the pancreas, particularly in ductal and islet cells, making it a specific target for regenerative medicine in endocrinology. Therapeutic strategies focusing on this receptor aim to reverse the progression of diabetes by addressing the underlying loss of insulin-producing cells.

Other names

Reg3A receptorReg receptorEXTL3 (Exostosin-like 3)INGAP-binding proteinRegenerating islet-derived protein 3-alpha receptor

Agonism of the receptor stimulates the differentiation of pancreatic ductal cells into insulin-secreting beta cells and promotes the proliferation of existing beta cells.