{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:31:17Z","timestamp":1792067477271,"version":"4.4.0"},"reference-count":45,"publisher":"American Diabetes Association","issue":"10","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,10,1]]},"abstract":"<jats:p>OBJECTIVE\u2014\u03b2-Cell response to glucose is characterized by mitochondrial membrane potential (\u0394\u03a8) hyperpolarization and the production of metabolites that serve as insulin secretory signals. We have previously shown that glucose-induced mitochondrial hyperpolarization accompanies the concentration-dependent increase in insulin secretion within a wide range of glucose concentrations. This observation represents the integrated response of a large number of mitochondria within each individual cell. However, it is currently unclear whether all mitochondria within a single \u03b2-cell represent a metabolically homogenous population and whether fuel or other stimuli can recruit or silence sizable subpopulations of mitochondria. This study offers insight into the different metabolic states of \u03b2-cell mitochondria.<\/jats:p>\n               <jats:p>RESULTS\u2014We show that mitochondria display a wide heterogeneity in \u0394\u03a8 and a millivolt range that is considerably larger than the change in millivolts induced by fuel challenge. Increasing glucose concentration recruits mitochondria into higher levels of homogeneity, while an in vitro diabetes model results in increased \u0394\u03a8 heterogeneity. Exploration of the mechanism behind heterogeneity revealed that temporary changes in \u0394\u03a8 of individual mitochondria, ATP-hydrolyzing mitochondria, and uncoupling protein 2 are not significant contributors to \u0394\u03a8 heterogeneity. We identified BAD, a proapoptotic BCL-2 family member previously implicated in mitochondrial recruitment of glucokinase, as a significant factor influencing the level of heterogeneity.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014We suggest that mitochondrial \u0394\u03a8 heterogeneity in \u03b2-cells reflects a metabolic reservoir recruited by an increased level of fuels and therefore may serve as a therapeutic target.<\/jats:p>","DOI":"10.2337\/db06-0757","type":"journal-article","created":{"date-parts":[[2007,9,5]],"date-time":"2007-09-05T21:00:14Z","timestamp":1189026014000},"page":"2569-2578","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":99,"title":["\u03b2-Cell Mitochondria Exhibit Membrane Potential Heterogeneity That Can Be Altered by Stimulatory or Toxic Fuel Levels"],"prefix":"10.2337","volume":"56","author":[{"given":"Jakob D.","family":"Wikstrom","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shana M.","family":"Katzman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hibo","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilad","family":"Twig","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon A.","family":"Graf","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Heart","sequence":"additional","affiliation":[{"name":"Obesity Research Center, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.A.","family":"Molina","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara E.","family":"Corkey","sequence":"additional","affiliation":[{"name":"Obesity Research Center, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina Moitoso","family":"de Vargas","sequence":"additional","affiliation":[{"name":"Obesity Research Center, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nika N.","family":"Danial","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Collins","sequence":"additional","affiliation":[{"name":"Division of Translational Biology, Endocrine Biology Program, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orian S.","family":"Shirihai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031208235314400_R1","doi-asserted-by":"crossref","unstructured":"Duchen MR: Roles of mitochondria in health and disease. 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