We are constantly looking to further our fundamental understanding of type 2 diabetes (T2DM), to combat its increasing global impact on health. One area of investigation is the connection between insulin resistance and cellular damage, specifically in relation to stress in the endoplasmic reticulum (ER). Excessive insulin folding is considered a harmful driver of β-cell dysfunction through the development of ER stress and oxidative stress.

In this novel study, Vidrio-Huerta and colleagues developed an experimental cell model with an inducible system for human insulin expression (Tet-On INS), for glucose-independent induction of insulin synthesis. Using this model, they examined the effects of elevated insulin folding, distinctive for the compensatory phase of early T2DM, on luminal H₂O₂ generation, ER stress, cell viability and cell dysfunction. The paper also highlights some very nice fluorescence work, and a number of images are included to confirm the findings, which is always a joy to see!

Elevated insulin synthesis was shown to increase H₂O₂ generation inside the ER, which was abolished by ER catalase. This supports the theory that insulin elevation alone causes insult to cells, which could lead to early resistance. This finding may play a pivotal role in the diagnosis and treatment of early T2DM.

Read the full article in Journal of Molecular Endocrinology 72 e230087 https://doi.org/10.1530/JME-23-0087