A study of the laboratory of Angela M. Valverde (IIBM-CSIC) recently published in Diabetologia has shown that small extracellular vesicles (sEV) released by the hepatocytes under toxic excess fat – known as lipotoxicity – induces inflammation and dysfunction in the pancreas, contributing to the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) and the development of type 2 diabetes. These small particles have previously been linked to liver inflammation and the progression of MASLD, but their impact on extrahepatic tissues such as the pancreas was not known in detail.

This study has provided evidence of liver and pancreas inflammation and beta cell dysfunction induced by lipotoxic hepatocyte-released sEV. The results also envision TLR4-mediated signalling in islet macrophages as a key mediator of the effects of lipotoxic sEV on beta cell function.