Lipid Droplets' Role in the Regulation of β-Cell Function and β-Cell Demise in Type 2 Diabetes

During development of type 2 diabetes (T2D), excessive nutritional load is thought to expose pancreatic islets to toxic effects of lipids and reduce beta-cell function and mass. However, lipids also play a positive role in cellular metabolism and function. Thus, proper trafficking of lipids is critical for beta cells to maximize the beneficial effects of these molecules while preventing their toxic effects. Lipid droplets (LDs) are organelles that play an important role in the storage and trafficking of lipids. In this review, we summarize the discovery of LDs in pancreatic beta cells, LD lifecycle, and the effect of LD catabolism on beta-cell insulin secretion. We discuss factors affecting LD formation such as age, cell type, species, and nutrient availability. We then outline published studies targeting critical LD regulators, primarily in rat and human beta-cell models, to understand the molecular effect of LD formation and degradation on beta-cell function and health. Furthermore, based on the abnormal LD accumulation observed in human T2D islets, we discuss the possible role of LDs during the development of beta-cell failure in T2D. Current knowledge indicates that proper formation and clearance of LDs are critical to normal insulin secretion, endoplasmic reticulum homeostasis, and mitochondrial integrity in beta cells. However, it remains unclear whether LDs positively or negatively affect human beta-cell demise in T2D. Thus, we discuss possible research directions to address the knowledge gap regarding the role of LDs in beta-cell failure.

Automated summary

This review summarizes the role of lipid droplets (LDs) in pancreatic beta cells and their impact on beta-cell function and health. Proper formation and clearance of LDs are critical for insulin secretion, endoplasmic reticulum homeostasis, and mitochondrial integrity in beta cells. However, the effect of LDs on human beta-cell demise in type 2 diabetes (T2D) is still unclear.