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A Clinically Applicable Positive Allosteric Modulator of GABA Receptors Promotes Human β-Cell Replication and Survival as well as GABA’s Ability to Inhibit Inflammatory T Cells
Joint Authors
Tian, Jide
Dang, Hoa
Karashchuk, Nataliya
Xu, Irvin
Kaufman, Daniel L.
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-7, 7 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-02-26
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Abstract EN
A major goal of T1D research is to develop new approaches to increase β-cell mass and control autoreactive T cell responses.
GABAA-receptors (GABAA-Rs) are promising drug targets in both those regards due to their abilities to promote β-cell replication and survival, as well as inhibit autoreactive T cell responses.
We previously showed that positive allosteric modulators (PAMs) of GABAA-Rs could promote rat β-cell line INS-1 and human islet cell replication in vitro.
Here, we assessed whether treatment with alprazolam, a widely prescribed GABAA-R PAM, could promote β-cell survival and replication in human islets after implantation into NOD/scid mice.
We observed that alprazolam treatment significantly reduced human islet cell apoptosis following transplantation and increased β-cell replication in the xenografts.
Evidently, the GABAA-R PAM works in conjunction with GABA secreted from β-cells to increase β-cell survival and replication.
Treatment with both the PAM and GABA further enhanced human β-cell replication.
Alprazolam also augmented the ability of suboptimal doses of GABA to inhibit antigen-specific T cell responses in vitro.
Thus, combined GABAA-R agonist and PAM treatment may help control inflammatory immune responses using reduced drug dosages.
Together, these findings suggest that GABAA-R PAMs represent a promising drug class for safely modulating islet cells toward beneficial outcomes to help prevent or reverse T1D and, together with a GABAA-R agonist, may have broader applications for ameliorating other disorders in which inflammation contributes to the disease process.
American Psychological Association (APA)
Tian, Jide& Dang, Hoa& Karashchuk, Nataliya& Xu, Irvin& Kaufman, Daniel L.. 2019. A Clinically Applicable Positive Allosteric Modulator of GABA Receptors Promotes Human β-Cell Replication and Survival as well as GABA’s Ability to Inhibit Inflammatory T Cells. Journal of Diabetes Research،Vol. 2019, no. 2019, pp.1-7.
https://search.emarefa.net/detail/BIM-1173069
Modern Language Association (MLA)
Tian, Jide…[et al.]. A Clinically Applicable Positive Allosteric Modulator of GABA Receptors Promotes Human β-Cell Replication and Survival as well as GABA’s Ability to Inhibit Inflammatory T Cells. Journal of Diabetes Research No. 2019 (2019), pp.1-7.
https://search.emarefa.net/detail/BIM-1173069
American Medical Association (AMA)
Tian, Jide& Dang, Hoa& Karashchuk, Nataliya& Xu, Irvin& Kaufman, Daniel L.. A Clinically Applicable Positive Allosteric Modulator of GABA Receptors Promotes Human β-Cell Replication and Survival as well as GABA’s Ability to Inhibit Inflammatory T Cells. Journal of Diabetes Research. 2019. Vol. 2019, no. 2019, pp.1-7.
https://search.emarefa.net/detail/BIM-1173069
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1173069