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FB2026_01
,
released March 12, 2026
Work in flies has allowed identification of a candidate polypeptide hormone in humans that acts as a "decretin," a hormone induced by fasting that suppresses insulin production or secretion (the reverse of incretins, which up-regulate insulin secretion in response to increased glucose). Dmel\Lst has been determined to act in this capacity in Drosophila; classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for this gene. Based on interactions with orthologous hormone receptors and similar roles in regulation of insulin release, Dmel\Lst is postulated to be functionally equivalent to human NMU. A 15-aa Lst-derived peptide appears to be functionally equivalent to NMU-25.
The human NMU gene has not been introduced into flies. The fly gene PK1-R is postulated to be a receptor for the Lst-derived peptide; it is orthologous to human NMUR1 and NMUR2 (neuromedin U receptors).
Expression of Lst is induced in gut-associated endocrine corpora cardiaca cells by carbohydrate restriction. Animals homozygous for an amorphic mutation of Lst are hypoglycemic, obese (based on triglyceride content) and short-lived. There is a single genetic interaction described for Dmel\Lst; see the Lst gene report.
[updated Feb. 2017 by FlyBase; FBrf0222196]
NMU is associated with Adiponectin levels and with body fat distribution in GWAS studies (see GWAS Catalog, below in 'External links').
The NMU gene encodes a member of the neuromedin family of neuropeptides. The encoded protein is a precursor that is proteolytically processed to generate a biologically active neuropeptide (NMU-25) that plays a role in pain, stress, immune-mediated inflammatory diseases and feeding regulation. [from Gene Cards, NMU; 2017.02.21]
Many to many: multiple paralogous and orthologous genes in both species.
Many to many: multiple paralogous and orthologous genes in both species.
There is evidence for functional equivalence of Dmel\Lst and human NMU; a 15-aa Lst-derived peptide appears to be functionally equivalent to NMU-25. (FBrf0227467)
Moderate-scoring ortholog of human NMUR1 and NMUR2; multiple paralogous and orthologous genes in both species (many Drosophila to many human). Dmel\PK1-R shares 33-34% identity and 49-53% similarity with human NMUR1 and NMUR2.
Based on interactions with orthologous hormone receptors and similar roles in regulation of insulin release, Dmel\Lst has been determine to be functionally equivalent to human NMU. A 15-aa Lst-derived peptide appears to be functionally equivalent to NMU-25. (FBrf0227467)