Lipids play essential roles in pancreatic β-cells, influencing both their physiology and their responses to metabolic stress. In these insulin-secreting cells, lipids are not only key signaling molecules and membrane components but also critical to cellular health. β-cells lacking adequate lipid reserves are unable to secrete insulin effectively. Lipids and lipid-derived molecules act as metabolic coupling factors, amplifying glucose-stimulated insulin secretion. As vital components of cellular membranes, lipids shape membrane structure and fluidity, affecting insulin secretory vesicles and the plasma membrane—where they regulate receptors and ion channels crucial for glucose sensing and insulin release.
Central to β-cell lipid metabolism is the glycerolipid/non-esterified fatty acids (NEFA) cycle, which includes both lipogenic and lipolytic pathways. The lipogenic branch supplies triacylglycerols stored in lipid droplets, a process that shields β-cells from lipotoxicity and oxidative stress. Lipid droplets, indispensable for optimal insulin secretion, not only store lipids but also act as dynamic organelles, regulating energy homeostasis by balancing lipogenesis and lipolysis.
Under pathological conditions, high glucose and lipid levels (glucolipotoxicity) intensify lipid accumulation and oxidative stress, driving β-cell dysfunction and insulin resistance. In the presence of hyperglycemia, lipotoxicity also alters the lipid composition in β-cell membranes, disrupting cell signaling, increasing inflammation, and impairing insulin secretion—all of which contribute to the progression of type 2 diabetes.
Aims of the projects:
- Exploring the Interplay Between Glucose and Lipid Metabolism in Pancreatic β-Cells
- Investigating Redox Regulation in Lipid Metabolism of Pancreatic β-Cells
- Examining the Function of Lipid Droplets in Pancreatic β-Cell Health
- Lipidomic Profiling to Uncover Lipid Dynamics in Pancreatic β-Cells
Fig.: Synthesis of lipid droplets in pancreatic β-cells under variuous nutritional conditions
