Logo image
Lipid Droplets' Role in the Regulation of β-Cell Function and β-Cell Demise in Type 2 Diabetes
Journal article   Open access   Peer reviewed

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

Xin Tong, Siming Liu, Roland Stein and Yumi Imai
Endocrinology (Philadelphia), Vol.163(3), bqac007
03/01/2022
DOI: 10.1210/endocr/bqac007
PMCID: PMC8826878
PMID: 35086144
url
https://doi.org/10.1210/endocr/bqac007View
Published (Version of record) Open Access

Abstract

During development of type 2 diabetes (T2D), excessive nutritional load is thought to expose pancreatic islets to toxic effects of lipids and reduce β-cell function and mass. However, lipids also play a positive role in cellular metabolism and function. Thus, proper trafficking of lipids is critical for β 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 β cells, LD lifecycle, and the effect of LD catabolism on β-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 β-cell models, to understand the molecular effect of LD formation and degradation on β-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 β-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 β cells. However, it remains unclear whether LDs positively or negatively affect human β-cell demise in T2D. Thus, we discuss possible research directions to address the knowledge gap regarding the role of LDs in β-cell failure.
Animals Cell Death Cellular Senescence Diabetes Mellitus, Type 2 - pathology Diabetes Mellitus, Type 2 - physiopathology Endoplasmic Reticulum Stress Humans Insulin Secretion - physiology Insulin-Secreting Cells - physiology Insulin-Secreting Cells - ultrastructure Lipid Droplets - physiology Perilipin-2 - physiology Perilipin-5 - physiology Rats

Details

Metrics

Logo image