Genetics and molecular biology: HDL-endoplasmic reticulum connection and cholesterol sensor

摘要

There is accumulating evidence indicating that HDLs improve the functionality of pancreatic beta cells and the insulin sensitivity of peripheral tissues (e.g. skeletal muscle and liver). A very recent review discusses the data supporting a protective role of HDLs in these tissues and the consequence that this may have on diabetes development. Oddly, this review does not mention the now amply demonstrated antiapoptotic function exerted by HDLs on pancreatic beta cells. As beta cell apoptosis contributes to the development of type 2 diabetes , understanding the prosurvival function of HDLs in beta cells is of particular importance. A study published a few months ago uncovered a link between HDL and the functionality of the endoplas-mic reticulum (ER) in beta cells. This work shows that HDLs prevent beta cell death induced by various ER stressors, such as palmitate, ER overload, or the sarco-endoplasmic reticulum Ca~(2+)-ATPase (SERCA) inhibitor thapsigargin, by maintaining the functionality of the ER in terms of protein folding and protein trafficking. This is of interest because ER stress is a likely important contributor to the development of type 2 diabetes.