Diabetes is the most common endocrine disorder, expected to affect over 365 million people worldwide by 2030, with type 2 diabetes (T2D) being the most prevalent. Glucose is the main energy source for our bodies. After eating, blood glucose levels rise temporarily. Hormones like GLP-1 from the gut and insulin from the pancreas help restore these levels. GLP-1 prompts the pancreas to release insulin, which signals various organs to absorb glucose, maintaining balanced levels. In diabetics, this process often malfunctions. Hormones are produced as precursor molecules called prohormones in the endoplasmic reticulum (ER) and processed in the Golgi apparatus. Secretory granules containing these prohormones form from the Golgi and mature into vesicles that store the hormones until needed. Actin, a protein forming part of the cell’s skeleton, creates a network that holds these granules in place until they are ready to be released. We have identified a crucial protein that remodels the actin network, essential for the secretion of GLP-1 and insulin. Removing this protein, both in living organisms and cell cultures, impairs hormone secretion, highlighting its importance in regulating glucose levels. This project aims to fill a significant gap in understanding how actin-remodelling proteins control glucose levels. By conducting a targeted drug screen, we hope to identify new therapies leveraging this mechanism to treat T2D potentially leading to better glucose management for diabetics.

2025