The role of phospholipid metabolism in type 2 diabetes development

Type 2 diabetes (T2D) is a global pandemic and has for long been considered an irreversible disease.

However, recent studies have shown that T2D remission is possible and, similar to T2D development, closely linked with lipids accumulated in non-adipose tissues, such as pancreas and skeletal muscle. T2D develops due to a combined decrease in tissue insulin sensitivity and relative insulin secretion.

Although debatable, diacylglycerols (DAG) and ceramides are considered the root-cause of lipid-mediated alteration in insulin sensitivity and secretion but the mechanism are unclear and masked with contradictive results due to limited data on the chemical diversity of lipids.

Of importance is that phospholipid hydrolysis is an important regulator of bioactive lipids such as ceramide and DAG.This project is therefore focused on phospholipid metabolism as a mediator of altered skeletal muscle insulin sensitivity and pancreatic islet insulin secretion.

To achieve this, a comprehensive approach is outlined where phospholipid derivatives will be characterized in human and rodent; 1) skeletal muscle, 2) pancreatic islets of Langerhans, and 3) in the circulation.

The aim is to identify lipids that are actively involved in T2D development and in particular those that can serve as therapeutic targets and risk markers to aid in T2D remission and disease preventionfor this global health threat.