{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:18:05Z","timestamp":1789906685266,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T00:00:00Z","timestamp":1551139200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008871","name":"Juvenile Diabetes Research Foundation","doi-asserted-by":"crossref","award":["2-SRA-2015-61-Q-R"],"award-info":[{"award-number":["2-SRA-2015-61-Q-R"]}],"id":[{"id":"10.13039\/100008871","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2019,2,26]]},"abstract":"<jats:p>A major goal of T1D research is to develop new approaches to increase <jats:italic>\u03b2<\/jats:italic>-cell mass and control autoreactive T cell responses. GABA<jats:sub>A<\/jats:sub>-receptors (GABA<jats:sub>A<\/jats:sub>-Rs) are promising drug targets in both those regards due to their abilities to promote <jats:italic>\u03b2<\/jats:italic>-cell replication and survival, as well as inhibit autoreactive T cell responses. We previously showed that positive allosteric modulators (PAMs) of GABA<jats:sub>A<\/jats:sub>-Rs could promote rat <jats:italic>\u03b2<\/jats:italic>-cell line INS-1 and human islet cell replication <jats:italic>in vitro<\/jats:italic>. Here, we assessed whether treatment with alprazolam, a widely prescribed GABA<jats:sub>A<\/jats:sub>-R PAM, could promote <jats:italic>\u03b2<\/jats:italic>-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 <jats:italic>\u03b2<\/jats:italic>-cell replication in the xenografts. Evidently, the GABA<jats:sub>A<\/jats:sub>-R PAM works in conjunction with GABA secreted from <jats:italic>\u03b2<\/jats:italic>-cells to increase <jats:italic>\u03b2<\/jats:italic>-cell survival and replication. Treatment with both the PAM and GABA further enhanced human <jats:italic>\u03b2<\/jats:italic>-cell replication. Alprazolam also augmented the ability of suboptimal doses of GABA to inhibit antigen-specific T cell responses <jats:italic>in vitro<\/jats:italic>. Thus, combined GABA<jats:sub>A<\/jats:sub>-R agonist and PAM treatment may help control inflammatory immune responses using reduced drug dosages. Together, these findings suggest that GABA<jats:sub>A<\/jats:sub>-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 GABA<jats:sub>A<\/jats:sub>-R agonist, may have broader applications for ameliorating other disorders in which inflammation contributes to the disease process.<\/jats:p>","DOI":"10.1155\/2019\/5783545","type":"journal-article","created":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T18:48:13Z","timestamp":1551206893000},"page":"1-7","source":"Crossref","is-referenced-by-count":20,"title":["A Clinically Applicable Positive Allosteric Modulator of GABA Receptors Promotes Human <i>\u03b2<\/i>-Cell Replication and Survival as well as GABA\u2019s Ability to Inhibit Inflammatory T Cells"],"prefix":"10.1155","volume":"2019","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5127-0970","authenticated-orcid":true,"given":"Jide","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoa","family":"Dang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliya","family":"Karashchuk","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irvin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, University of California, Los Angeles, 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