Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2016

Investigating the role of the System-L amino acid transporter LAT1 in the development of pancreatic beta-cell dysfunction and type 2 diabetes (#208)

Cherubina Ratnam 1 , Stanley Chan 1 , Ross Laybutt 2 , Terence P Herbert 1
  1. RMIT, Bundoora, VIC, Australia
  2. 2Garvan Institute of Medical Research, Sydney, NSW, Australia

In pancreatic beta-cells the branched-chain amino acids (BCAA) play an important role in cellular signaling, metabolism and insulin secretion. In this study, we demonstrate that the System-L BCAA transporter, LAT1, is abundantly expressed in islets of Langerhans and beta-cells and that increased LAT1 expression in islets correlates with disease progression in the db/db mouse model of diabetes. This increase in LAT1 expression may well be an important driver of ER stress induced beta-cell dysfunction in type-2 diabetes as we also show that ER stress selectively increases LAT1 expression in pancreatic beta-cells and that increased BCAA uptake exacerbates ER stress induced beta-cell death. To define the role of LAT1 in beta-cell dysfunction we have generated beta-cell specific inducible LAT1 knock-out mice. These mice are currently being characterised and the effect of LAT1 knock out on beta-cell function and the development of diabetes are being determined.