Urocortin-3 (UCN3)

Urocortin-3 is a 38-41 amino acid peptide hormone encoded by the *UCN3* gene and is a member of the corticotropin-releasing hormone (CRF) family[1][5]. It is expressed in the pancreas (mainly by beta cells but also alpha cells in humans), where it acts locally to stimulate somatostatin secretion from neighboring delta cells by activating CRF receptor type 2 (CRHR2), regulating insulin and glucagon release and thus playing a vital role in glucose homeostasis[2][5]. Urocortin-3 is also present in specific brain regions involved in the neural stress response and may modulate appetite and social memory via the central CRHR2 receptor[2][6]. In muscle, experimental overexpression has shown enhancement in insulin signaling, glucose transport, and muscle fiber diameter—suggesting potential roles in muscle metabolism and resistance to insulin resistance[4]. Urocortin-3 serves as a marker for beta cell maturity and is downregulated in beta cell dysfunction or dedifferentiation[2]. There are currently no approved drugs targeting Urocortin-3 directly; its roles in disease and therapeutic targeting are primarily under investigation.

Other names

UCN3StresscopinUrocortin IIIUrocortin 3

Endogenous: Activates corticotropin releasing hormone receptor 2 (CRHR2), a G protein-coupled receptor, leading to cAMP production and downstream hormone secretion[2][5]. Experimental: Overexpression enhances insulin signaling and skeletal muscle glucose uptake via PI3K/AKT and AMPK pathways[4].