CD28 and lupus nephritis: Since CD28 costimulation through phosphatidylinositol 3’-kinase (PI3K) and Akt is required for T cells to increase glucose uptake and glycolysis, the combination of CTLA4Ig, inhibitor for CD28 signaling, and metformin decreased the development of lupus nephritis in (NZB x NZW)F1 mice treated at the early stage of disease [69].