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The loss of glucose homoeostasis can arise from a loss of <jats:italic>\u03b2<\/jats:italic>-cell mass because of immune-cell-mediated attack, as in type 1 diabetes, and\/or from dysfunction of individual <jats:italic>\u03b2<\/jats:italic>-cells (in conjunction with target organ insulin resistance), as in type 2 diabetes. A better understanding of the transcriptional pathways regulating islet-cell survival is of great importance for the development of therapeutic strategies that target <jats:italic>\u03b2<\/jats:italic>-cells for diabetes. To this end, we previously identified the transcription factor <jats:italic>Myt3<\/jats:italic> as a pro-survival factor in islets following acute suppression of <jats:italic>Myt3 in vitro<\/jats:italic>. To determine the effects of <jats:italic>Myt3<\/jats:italic> suppression on islet-cell survival <jats:italic>in vivo<\/jats:italic>, we used an adenovirus to express an shRNA targeting <jats:italic>Myt3<\/jats:italic> in syngeneic optimal and marginal mass islet transplants, and demonstrate that suppression of <jats:italic>Myt3<\/jats:italic> impairs the function of marginal mass grafts. Analysis of grafts 5 weeks post-transplant revealed that grafts transduced with the sh<jats:italic>Myt3<\/jats:italic> adenovirus contained ~20% the number of transduced cells as grafts transduced with a control adenovirus. In fact, increased apoptosis and significant cell loss in the sh<jats:italic>Myt3<\/jats:italic>-transduced grafts was evident after only 5 days, suggesting that <jats:italic>Myt3<\/jats:italic> suppression sensitizes islet cells to stresses present in the early post-transplant period. Specifically, we find that <jats:italic>Myt3<\/jats:italic> suppression sensitizes islet cells to high glucose-induced cell death via upregulation of the pro-apoptotic Bcl2 family member Bim. Taken together these data suggest that Myt3 may be an important link between glucotoxic and immune signalling pathways.<\/jats:p>","DOI":"10.1038\/cddis.2016.141","type":"journal-article","created":{"date-parts":[[2016,5,21]],"date-time":"2016-05-21T00:22:26Z","timestamp":1463790146000},"page":"e2233-e2233","update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Myt3 suppression sensitizes islet cells to high glucose-induced cell death via Bim induction"],"prefix":"10.1038","volume":"7","author":[{"given":"B R","family":"Tennant","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Vanderkruk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Dhillon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C B","family":"Verchere","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B G","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,5,19]]},"reference":[{"key":"BFcddis2016141_CR1","doi-asserted-by":"publisher","first-page":"a007641","DOI":"10.1101\/cshperspect.a007641","volume":"2","author":"MA Atkinson","year":"2012","unstructured":"Atkinson MA . 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