A novel paradigm in islet regulation: microRNA control of α- and β-cells during development of type 2 diabetes

Type 2 diabetes (T2D) is a global health issue, impacting countless lives worldwide.

The role of microRNAs (miRNAs) in the regulation of insulin and glucagon secretion represents a domain replete with unexplored avenues.

This project attempts to bridge these knowledge gaps, shedding light on the complex interplay of miRNAs within human α- and β-cells during the onset and progression of T2D, thereby making a substantial contribution to diabetes research.The project is structured into three work packages.

Initially, we will employ single cell small RNA sequencing and proteomics to construct a comprehensive map of human miRNA-target interactions in α- and β-cells.

This will offer valuable insights into the cell-specific dynamic alterations in miRNA expression during disease progression, utilizing cutting-edge bioinformatic methodologies for optimal data analysis.Subsequently, we will scrutinize the release of exosomes in β-cells employing light-sheet and super-resolution microscopy techniques.

Exosomes will be purified from α- and β-cell medium, their miRNA content assessed, and the role of these miRNAs in intra-islet communication and crosstalk from cells of other metabolic tissues will be thoroughly investigated.Lastly, we will explore the potential of miRNA inhibitors to enhance insulin secretion in vivo using a rodent model of diabetes.This research is expected to pave the way for innovative therapeutic strategies for T2D.