{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:19:16Z","timestamp":1790201956828,"version":"4.1.0"},"reference-count":67,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,7,1]]},"abstract":"<jats:p>Mitochondrial glucose metabolism is essential for stimulated insulin release from pancreatic \u03b2-cells. Whether mitofusin gene expression, and hence, mitochondrial network integrity, is important for glucose or incretin signaling has not previously been explored. Here, we generated mice with \u03b2-cell\u2013selective, adult-restricted deletion knock-out (dKO) of the mitofusin genes Mfn1 and Mfn2 (\u03b2Mfn1\/2 dKO). \u03b2Mfn1\/2-dKO mice displayed elevated fed and fasted glycemia and a more than fivefold decrease in plasma insulin. Mitochondrial length, glucose-induced polarization, ATP synthesis, and cytosolic and mitochondrial Ca2+ increases were all reduced in dKO islets. In contrast, oral glucose tolerance was more modestly affected in \u03b2Mfn1\/2-dKO mice, and glucagon-like peptide 1 or glucose-dependent insulinotropic peptide receptor agonists largely corrected defective glucose-stimulated insulin secretion through enhanced EPAC-dependent signaling. Correspondingly, cAMP increases in the cytosol, as measured with an Epac-camps\u2013based sensor, were exaggerated in dKO mice. Mitochondrial fusion and fission cycles are thus essential in the \u03b2-cell to maintain normal glucose, but not incretin, sensing. These findings broaden our understanding of the roles of mitofusins in \u03b2-cells, the potential contributions of altered mitochondrial dynamics to diabetes development, and the impact of incretins on this process.<\/jats:p>","DOI":"10.2337\/db21-0800","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T17:03:38Z","timestamp":1650992618000},"page":"1472-1489","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":31,"title":["Mitofusins\n                    <i>Mfn1<\/i>\n                    and\n                    <i>Mfn2<\/i>\n                    Are Required to Preserve Glucose- but Not Incretin-Stimulated \u03b2-Cell Connectivity and Insulin Secretion"],"prefix":"10.2337","volume":"71","author":[{"given":"Eleni","family":"Georgiadou","sequence":"first","affiliation":[{"name":"1Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charanya","family":"Muralidharan","sequence":"additional","affiliation":[{"name":"2Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Martinez","sequence":"additional","affiliation":[{"name":"2Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Chabosseau","sequence":"additional","affiliation":[{"name":"1Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Akalestou","sequence":"additional","affiliation":[{"name":"1Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2290-8453","authenticated-orcid":false,"given":"Alejandra","family":"Tomas","sequence":"additional","affiliation":[{"name":"1Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona Yong Su","family":"Wern","sequence":"additional","affiliation":[{"name":"3Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodoros","family":"Stylianides","sequence":"additional","affiliation":[{"name":"4Centre of Innovative and Collaborative Construction Engineering, Loughborough University, Leicestershire, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6083-5227","authenticated-orcid":false,"given":"Asger","family":"Wretlind","sequence":"additional","affiliation":[{"name":"5Systems Medicin, Steno Diabetes Center Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Legido-Quigley","sequence":"additional","affiliation":[{"name":"5Systems Medicin, Steno Diabetes Center Copenhagen, Copenhagen, Denmark"},{"name":"6Institute of Pharmaceutical Science, Kings College London, London, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Jones","sequence":"additional","affiliation":[{"name":"7Section of Endocrinology and Investigative Medicine, Imperial College, London, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Lopez-Noriega","sequence":"additional","affiliation":[{"name":"1Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwen","family":"Xu","sequence":"additional","affiliation":[{"name":"8Department of Cell and Developmental Biology, Program of Developmental Biology, and Vanderbilt Center for Stem Cell Biology, Vanderbilt University, School of Medicine, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0772-9139","authenticated-orcid":false,"given":"Guoqiang","family":"Gu","sequence":"additional","affiliation":[{"name":"8Department of Cell and Developmental Biology, Program of Developmental Biology, and Vanderbilt Center for Stem Cell Biology, Vanderbilt University, School of Medicine, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour","family":"Alsabeeh","sequence":"additional","affiliation":[{"name":"9Department of Physiology, Health Sciences Center, Kuwait University, Kuwait City, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Cruciani-Guglielmacci","sequence":"additional","affiliation":[{"name":"10Regulation of Glycemia by Central Nervous System, Universit\u00e9 de Paris, BFA, UMR 8251, CNRS, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Magnan","sequence":"additional","affiliation":[{"name":"10Regulation of Glycemia by Central Nervous System, Universit\u00e9 de Paris, BFA, UMR 8251, CNRS, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Ibberson","sequence":"additional","affiliation":[{"name":"11Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Leclerc","sequence":"additional","affiliation":[{"name":"1Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf","family":"Ali","sequence":"additional","affiliation":[{"name":"3Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6777-4498","authenticated-orcid":false,"given":"Scott A.","family":"Soleimanpour","sequence":"additional","affiliation":[{"name":"12Division of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI"},{"name":"13Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, 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U.K"},{"name":"3Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"},{"name":"15Centre of Research of Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al (CHUM), University of Montreal, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2022,4,26]]},"reference":[{"key":"2023052414105347100_B1","doi-asserted-by":"crossref","first-page":"190126","DOI":"10.1098\/rsob.190126","article-title":"Mitochondria-hubs for regulating cellular biochemistry: emerging concepts and networks","volume":"9","author":"Anderson","year":"2019","journal-title":"Open Biol"},{"key":"2023052414105347100_B2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1042\/BJ20141384","article-title":"Pancreatic \u03b2-cell identity, glucose sensing and the control of insulin secretion","volume":"466","author":"Rutter","year":"2015","journal-title":"Biochem 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