{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:10:51Z","timestamp":1791472251031,"version":"4.3.4"},"reference-count":21,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":3453,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,4,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Although loss of functional \u03b2-cell mass is a hallmark of diabetes, no treatment approaches that halt this process are currently available. We recently identified thioredoxin-interacting protein (TXNIP) as an attractive target in this regard. Glucose and diabetes upregulate \u03b2-cell TXNIP expression, and TXNIP overexpression induces \u03b2-cell apoptosis. In contrast, genetic ablation of TXNIP promotes endogenous \u03b2-cell survival and prevents streptozotocin (STZ)- and obesity-induced diabetes. Finding an oral medication that could inhibit \u03b2-cell TXNIP expression would therefore represent a major breakthrough. We were surprised to discover that calcium channel blockers inhibited TXNIP expression in INS-1 cells and human islets and that orally administered verapamil reduced TXNIP expression and \u03b2-cell apoptosis, enhanced endogenous insulin levels, and rescued mice from STZ-induced diabetes. Verapamil also promoted \u03b2-cell survival and improved glucose homeostasis and insulin sensitivity in BTBR ob\/ob mice. Our data further suggest that this verapamil-mediated TXNIP repression is conferred by reduction of intracellular calcium, inhibition of calcineurin signaling, and nuclear exclusion and decreased binding of carbohydrate response element\u2013binding protein to the E-box repeat in the TXNIP promoter. Thus, for the first time, we have identified an oral medication that can inhibit proapoptotic \u03b2-cell TXNIP expression, enhance \u03b2-cell survival and function, and prevent and even improve overt diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db11-0955","type":"journal-article","created":{"date-parts":[[2012,3,23]],"date-time":"2012-03-23T08:43:29Z","timestamp":1332492209000},"page":"848-856","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":231,"title":["Preventing \u03b2-Cell Loss and Diabetes With Calcium Channel Blockers"],"prefix":"10.2337","volume":"61","author":[{"given":"Guanlan","family":"Xu","sequence":"first","affiliation":[{"name":"Comprehensive Diabetes Center and Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqin","family":"Chen","sequence":"additional","affiliation":[{"name":"Comprehensive Diabetes Center and Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gu","family":"Jing","sequence":"additional","affiliation":[{"name":"Comprehensive Diabetes Center and Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anath","family":"Shalev","sequence":"additional","affiliation":[{"name":"Comprehensive Diabetes Center and Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2012,3,14]]},"reference":[{"key":"2022031210310218900_B1","doi-asserted-by":"crossref","first-page":"3695","DOI":"10.1210\/en.2002-220564","article-title":"Oligonucleotide microarray analysis of intact human pancreatic islets: identification of glucose-responsive genes and a highly regulated TGFbeta signaling pathway","volume":"143","author":"Shalev","year":"2002","journal-title":"Endocrinology"},{"key":"2022031210310218900_B2","doi-asserted-by":"crossref","first-page":"3581","DOI":"10.1096\/fj.08-111690","article-title":"Thioredoxin-interacting protein deficiency induces Akt\/Bcl-xL signaling and pancreatic beta-cell mass and protects against diabetes","volume":"22","author":"Chen","year":"2008","journal-title":"FASEB J"},{"key":"2022031210310218900_B3","doi-asserted-by":"crossref","first-page":"938","DOI":"10.2337\/db07-0715","article-title":"Thioredoxin-interacting 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