In clinical, the 'fatigue' of beta cells is a famous phenomenon from way back. Nowadays, researchers describe how glucolipotoxicity, endoplasmic reticulum (ER) stress and oxidative stress impair beta cell function. In 2012, Talchai et al. revealed the novel machinery of beta cell dysfunction in diabetes - dedifferentiation. It's a gradual process along with the progressive feature of diabetes, and in several reports, it's proven to be preventable by existing diabetic treatment. Previously, we showed that each diabetic treatment had a different effect on beta cell dedifferentiation. For instance, food restriction had more manifold good effects to restore beta cell gene expression than SGLT inhibitor. In the current study, we aimed to unveil the molecular mechanism of beta cell dedifferentiation. First, we investigated the microarray analysis of islet RNAs in food-restricted db/db mice. Compared to the control db/db, the islets of food-restricted group had higher expressions of genes related to matured beta cell markers and ER maintenance. On the other hand, Gene expressions related to cell stress, cell growth and cell division were lowered by calorie restriction. To understand more about the relationship between beta cell dedifferentiation and ER stress, we utilized the other obese mice model, ob/ob, which is known to have more moderate hyperglycemia than db/db. The other study group demonstrated that ER and oxidative stress markers were maintained in ob/ob islets than that in db/db (Chan, Diabetes 2013). We found that beta cell dedifferentiation markers, such as Aldh1a3 and Sox9, were also lowered in ob/ob. But it's still unknown, whether the dedifferentiated beta cells are feeble against the ER and oxidative stress, or, these stress triggers the beta cell dedifferentiation.


X. Lei: None. E. Ishida: None. E. Yamada: None. S. Okada: None. M. Yamada: None.

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