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FB2026_01
,
released March 12, 2026
Multiple studies in mice and flies have implicated inositol 1,4,5-trisphosphate receptors (ITPR or InsP3R) in glucose homeostasis (inositol triphosphate is usually abbreviated InsP3 or IP3). These molecules act as intracellular calcium release channels; inositol triphosphate receptor-mediated signaling is involved in many processes including cell migration, cell division, smooth muscle contraction, and neuronal signaling. There are three genes that encode inositol 1,4,5-trisphosphate receptors in human, ITPR1, ITPR2, ITPR3. All three human genes are implicated in disease (MIM:206700, MIM:606658, MIM:117360, MIM:106190); in particular, ITPR3 is implicated in susceptibility to diabetes mellitus, insulin-dependent (MIM:222100; FBhh0000479). There is a single orthologous gene in Drosophila, Itpr, for which classical loss-of-function alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated.
None of the human ITPR genes has been introduced into flies.
Animals homozygous for the more severe loss-of-function mutations of Dmel\Itpr die during larval or pupal stages; growth defects and inability to feed normally are observed during larval stages. Viable hypomorphic mutant animals exhibit loss of appetite control leading to excessive feeding (hyperphagia), excess body weight and fat deposits (on a normal diet), and increased starvation resistance. Lipid profiling shows a higher level of storage lipids (triacylglycerides) and a reduced level of membrane lipids, compared to control animals. Some, but not all, of the phenotypic effects are ameliorated by overexpression of the Drosophila insulin-like peptide Ilp2 in the insulin-producing cells (IPC) of the adult brain. Therapeutic drug assayed: both wild-type and mutant animals fed the lipase inhibitor, Orlistat, showed modestly reduced starvation resistance and triacylglyceride levels relative to untreated animals.
Genetic and physical interactions of Dmel\Itpr have been described; see below and in the gene report for Itpr.
[updated Feb. 2017 by FlyBase; FBrf0222196]
Obesity is an abnormal accumulation of body fat, usually 20% or more over an individual's ideal body weight. Obesity is associated with increased risk of illness, disability, and death. (http://medical-dictionary.thefreedictionary.com/obesity).
The development of obesity is recognized as having both genetic and environmental components (https://www.sciencelearn.org.nz/resources/203-obesity-genetic-or-environmental).
ITPR2 is associated with body fat distribution in multiple GWAS studies (see GWAS Catalog, below in 'External links').
ITPR3 is associated with extreme obesity in a GWAS study (see GWAS Catalog, below in 'External links').
Members of the ITPR family are second messenger intracellular calcium release channels; they mediate a rise in cytoplasmic calcium in response to extracellular-receptor-activated production of inositol triphosphate. IPTR1 mediates calcium release from the endoplasmic reticulum. Inositol triphosphate receptor-mediated signaling is involved in many processes including cell migration, cell division, smooth muscle contraction, and neuronal signaling. [from NCBI Gene, ITPR1, ITPR2; 2017.02.21]
Many to one (3 human to 1 Drosophila); the 3 human genes are ITPR1, ITPR2, and ITPR3.
Many to one (3 human to 1 Drosophila); the 3 human genes are ITPR1, ITPR2, and ITPR3.
Many to one (3 human to 1 Drosophila); the 3 human genes are ITPR1, ITPR2, and ITPR3.
High-scoring ortholog of human ITPR1; moderate-scoring ortholog of ITPR2 and ITPR3 (1 Drosophila to 3 human); Dmel\Itp-r83A shares 52-57% identity and 67-70% similarity with the human genes.