Cyb5r3 activation rescues secondary failure to sulfonylurea but not β-cell dedifferentiation.

Autor: Watanabe H; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.; Naomi Berrie Diabetes Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, United States of America., Asahara SI; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.; Naomi Berrie Diabetes Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.; Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan., Son J; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.; Naomi Berrie Diabetes Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, United States of America., McKimpson WM; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.; Naomi Berrie Diabetes Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, United States of America., de Cabo R; Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America., Accili D; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.; Naomi Berrie Diabetes Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Feb 09; Vol. 19 (2), pp. e0297555. Date of Electronic Publication: 2024 Feb 09 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0297555
Abstrakt: Diabetes mellitus is characterized by insulin resistance and β-cell failure. The latter involves impaired insulin secretion and β-cell dedifferentiation. Sulfonylurea (SU) is used to improve insulin secretion in diabetes, but it suffers from secondary failure. The relationship between SU secondary failure and β-cell dedifferentiation has not been examined. Using a model of SU secondary failure, we have previously shown that functional loss of oxidoreductase Cyb5r3 mediates effects of SU failure through interactions with glucokinase. Here we demonstrate that SU failure is associated with partial β-cell dedifferentiation. Cyb5r3 knockout mice show more pronounced β-cell dedifferentiation and glucose intolerance after chronic SU administration, high-fat diet feeding, and during aging. A Cyb5r3 activator improves impaired insulin secretion caused by chronic SU treatment, but not β-cell dedifferentiation. We conclude that chronic SU administration affects progression of β-cell dedifferentiation and that Cyb5r3 activation reverses secondary failure to SU without restoring β-cell dedifferentiation.
Competing Interests: Domenico Accili was a founder, director, and chair of the advisory board of Forkhead Therapeutics, Corp. He sits on the Global Diabetes Advisory Board of Eli Lilly & Co. The other authors declare that they have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
Databáze: MEDLINE
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