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Until recently, the decline of insulin production had been ascribed to \u03b2\u2010cell death. But recent research has shown that \u03b2\u2010cells do not die in diabetes, but undergo a silencing process, termed \u201cdedifferentiation.\u201d The main implication of this discovery is that \u03b2\u2010cells can be revived by appropriate treatments. We have shown that mitochondrial abnormalities are a key step in the progression of \u03b2\u2010cell dysfunction towards dedifferentiation. In normal \u03b2\u2010cells, mitochondria generate energy required to sustain insulin production and its finely timed release in response to the body's nutritional status. A normal \u03b2\u2010cell can adapt its mitochondrial fuel source based on substrate availability, a concept known as \u201cmetabolic flexibility.\u201d This capability is the first casualty in the progress of \u03b2\u2010cell failure. \u03b2\u2010Cells lose the ability to select the right fuel for mitochondrial energy production. Mitochondria become overloaded, and accumulate by\u2010products derived from incomplete fuel utilization. Energy production stalls, and insulin production drops, setting the stage for dedifferentiation. The ultimate goal of these investigations is to explore novel treatment paradigms that will benefit people with diabetes.<\/jats:p>","DOI":"10.1111\/dom.12723","type":"journal-article","created":{"date-parts":[[2016,9,12]],"date-time":"2016-09-12T06:26:08Z","timestamp":1473661568000},"page":"117-122","source":"Crossref","is-referenced-by-count":106,"title":["When \u03b2\u2010cells fail: lessons from dedifferentiation"],"prefix":"10.1111","volume":"18","author":[{"given":"D.","family":"Accili","sequence":"first","affiliation":[{"name":"Department of Medicine and Berrie Diabetes Center, Columbia University  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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