BioRxiv
bioRxiv Subject Collection: Systems Biology
This feed contains articles for bioRxiv Subject Collection "Systems Biology"
Compromised beta-cell identity in type 2 diabetes
Compromised beta-cell identity is emerging as an important contributor of beta-cell dysfunction in type 2 diabetes (T2D). Several studies suggest that hyperglycemia induces the inactivation of transcription factors involved in mature beta-cell identity. More specifically, chronic hyperglycemia leads to the downregulation of PDX1 and MAFA, two important beta-cell identity transcription factors and regulators of insulin promoter activity. Regulation of these transcription factors depends on interactions between multiple signaling cascades and processes driven by complex non-linear dynamics and taking place in different cellular compartments. To better understand these non-linear dynamics, we developed an integrated mathematical model of the underlying mechanisms regulating these key transcription factors. Our model was able to reproduce experimentally measured variations in the levels of PDX1, MAFA and insulin mRNA under different glucose concentrations. We used this model to simulate scenarios that could allow to restore PDX1 and MAFA levels and therefore insulin gene expression. From these simulations, FOXO1 emerged as an important target for the restoration of beta-cell identity.
Dutta, P., Merabet, N., Quax, R., Carlotti, F., Sloot, P. M. A.
March 24, 2023
http://biorxiv.org/cgi/content/short/2023.03.20.533468v1?rss=1