Diazepam binding inhibitor (DBI) is a 9-kD polypeptide that was first isolated in 1983 from rat brain by monitoring its ability to displace diazepam from the benzodiazepine (BZD) recognition site located on the extracellular domain of the type A receptor for gamma-aminobutyric acid (GABAA receptor) and from the mitochondrial BZD receptor (MBR) located on the outer mitochondrial membrane. In brain, DBI and its two major processing products [DBI 33-50, or octadecaneuropeptide (ODN) and DBI 17-50, or triakontatetraneuropeptide (TTN)] are unevenly distributed in neurons, with the highest concentrations of DBI (10 to 50 microMs) being present in the hypothalamus, amygdala, cerebellum, and discrete areas of the thalamus, hippocampus, and cortex.
Learning and memory are fundamental processes that are disrupted in many neurological disorders including Alzheimer's disease and epilepsy. The hippocampus plays an integral role in these functions, and modulation of synaptic transmission mediated by γ-aminobutyric acid (GABA) type-A receptors (GABAA Rs) impacts hippocampus-dependent learning and memory. The protein diazepam binding inhibitor (DBI) differentially modulates GABAA Rs in various brain regions, including hippocampus, and changes in DBI levels may be linked to altered learning and memory.
DBI is widely expressed in the central nervous system, and high concentrations have been found in areas involved in the control of feeding behavior. The biological effects of endozepines are mediated through three types of receptors: central-type benzodiazepine receptors (CBR), peripheral-type benzodiazepine receptors (PBR), and metabotropic receptors. It has been shown that injection of octadecaneuropeptide (ODN), which is a derivative of DBI, causes reduction in food consumption. Its anorexigenic effect is long-lasting, and leads to a substantial loss of weight.
Diazepam binding inhibitor is also known to mediate the feedback regulation of pancreatic secretion and the postprandial release of cholecystokinin, in addition to its role as a mediator in corticotropin-dependent adrenal steroidogenesis. Three pseudogenes located on chromosomes 6, 8 and 16 have been identified. Multiple transcript variants encoding different isoforms have been described for this gene.
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Differential impacts on multiple forms of spatial and contextual memory in diazepam binding inhibitor knockout mice. Ujjainwala AL, Courtney CD, Wojnowski NM, Rhodes JS, Christian CA. J Neurosci Res. 2019 Jan 25. doi: 10.1002/jnr.24393. [Epub ahead of print] PMID: 30680776
Subregion-Specific Impacts of Genetic Loss of Diazepam Binding Inhibitor on Synaptic Inhibition in the Murine Hippocampus. Courtney CD, Christian CA. Neuroscience. 2018 Sep 15;388:128-138. doi: 10.1016/j.neuroscience.2018.07.012. Epub 2018 Jul 19. PMID: 30031126 Free PMC Article
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Reduced plasma level of diazepam-binding inhibitor (DBI) in patients with morbid obesity. Siejka A, Jankiewicz-Wika J, Stępień H, Fryczak J, Świętosławski J, Komorowski J. Endocrine. 2015 Aug;49(3):859-62. doi: 10.1007/s12020-014-0522-5. Epub 2015 Jan 6. No abstract available. PMID: 25561371 Free PMC Article
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Cloning and tissue-specific functional characterization of the promoter of the rat diazepam binding inhibitor, a peptide with multiple biological actions. Kolmer M, Alho H, Costa E, Pani L. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8439-43. PMID: 7690962 Free PMC Article
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