Details

Autor(en) / Beteiligte

• Leenders, Floris
• Groen, Nathalie
• de Graaf, Natascha
• Engelse, Marten A
• Rabelink, Ton J
• de Koning, Eelco J P
• Carlotti, Françoise

Titel

Oxidative Stress Leads to β-Cell Dysfunction Through Loss of β-Cell Identity

Ist Teil von

• Frontiers in immunology, 2021-11, Vol.12, p.690379-690379

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Pancreatic β-cell failure is a critical event in the onset of both main types of diabetes mellitus but underlying mechanisms are not fully understood. β-cells have low anti-oxidant capacity, making them more susceptible to oxidative stress. In type 1 diabetes (T1D), reactive oxygen species (ROS) are associated with pro-inflammatory conditions at the onset of the disease. Here, we investigated the effects of hydrogen peroxide-induced oxidative stress on human β-cells. We show that primary human β-cell function is decreased. This reduced function is associated with an ER stress response and the shuttling of FOXO1 to the nucleus. Furthermore, oxidative stress leads to loss of β-cell maturity genes MAFA and PDX1, and to a concomitant increase in progenitor marker expression of SOX9 and HES1. Overall, we propose that oxidative stress-induced β-cell failure may result from partial dedifferentiation. Targeting antioxidant mechanisms may preserve functional β-cell mass in early stages of development of T1D.