ABCA12 regulates insulin secretion from beta-cells
Gloria M Ursino, Ying Fu, Denny L Cottle, Nigora Mukhamedova, Lynelle K Jones, Hann Low, Ming Shen Tham, Wan Jun Gan, Natalie A Mellett, Partha P Das, Jacquelyn M Weir, Michael Ditiatkovski, Stacey Fynch, Peter Thorn, Helen E Thomas, Peter J Meikle, Helena C Parkington, Ian M Smyth, Dmitri Sviridov
EMBO REPORTS | WILEY | Published : 2020
Dysregulation of lipid homeostasis is intimately associated with defects in insulin secretion, a key feature of type 2 diabetes. Here, we explore the role of the putative lipid transporter ABCA12 in regulating insulin secretion from β-cells. Mice with β-cell-specific deletion of Abca12 display impaired glucose-stimulated insulin secretion and eventual islet inflammation and β-cell death. ABCA12's action in the pancreas is independent of changes in the abundance of two other cholesterol transporters, ABCA1 and ABCG1, or of changes in cellular cholesterol or ceramide content. Instead, loss of ABCA12 results in defects in the genesis and fusion of insulin secretory granules and increases in the..View full abstract
Awarded by National Health and Medical Research Council of Australia
Awarded by National Health and Medical Research Council
The study was supported by the grants from the National Health and Medical Research Council of Australia (GNT1020281, GNT1036352, GNT1123554) and supported in part by the Victorian Government's OIS Program. The authors acknowledge the assistance of the Monash Microimaging Platform, Monash Animal Research Platform, Histology Platform and Monash FlowCore. IMS is supported by a Senior Research Fellowship of the National Health and Medical Research Council (APP1106516), and GMU acknowledges the support of an Australian Postgraduate Award.