التفاصيل البيبلوغرافية
| العنوان: |
Nrf2 Regulates β-Cell Mass by Suppressing β-Cell Death and Promoting β-Cell Proliferation. |
| المؤلفون: |
Baumel-Alterzon, Sharon, Katz, Liora S., Brill, Gabriel, Jean-Pierre, Clairete, Li, Yansui, Tse, Isabelle, Biswal, Shyam, Garcia-Ocaña, Adolfo, Scott, Donald K. |
| المصدر: |
Diabetes; 2022, Vol. 71 Issue 5, p989-1011, 23p |
| مصطلحات موضوعية: |
PROTEINS, STEROIDS, ANIMAL experimentation, DIABETES, APOPTOSIS, CELL physiology, ISLANDS of Langerhans, INSULIN, RESEARCH funding, GLUCOSE, MICE |
| مستخلص: |
Finding therapies that can protect and expand functional β-cell mass is a major goal of diabetes research. Here, we generated β-cell-specific conditional knockout and gain-of-function mouse models and used human islet transplant experiments to examine how manipulating Nrf2 levels affects β-cell survival, proliferation, and mass. Depletion of Nrf2 in β-cells results in decreased glucose-stimulated β-cell proliferation ex vivo and decreased adaptive β-cell proliferation and β-cell mass expansion after a high-fat diet in vivo. Nrf2 protects β-cells from apoptosis after a high-fat diet. Nrf2 loss of function decreases Pdx1 abundance and insulin content. Activating Nrf2 in a β-cell-specific manner increases β-cell proliferation and mass and improves glucose tolerance. Human islets transplanted under the kidney capsule of immunocompromised mice and treated systemically with bardoxolone methyl, an Nrf2 activator, display increased β-cell proliferation. Thus, by managing reactive oxygen species levels, Nrf2 regulates β-cell mass and is an exciting therapeutic target for expanding and protecting β-cell mass in diabetes. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
