Fig. 5. Induction of DN-SREBP-1c largely prevented chronic high-glucose-induced glucolipotoxicity in INS-1 cells. (A) DN-SREBP-1c diminished lipid droplets accumulation, as seen by staining with Oil Red-O. DN-SREBP-1c^*23 cells were cultured in either standard (11.2 mM; Control) or 30 mM glucose (High glucose) medium for 48 hours, in the presence (+Dox) or absence (-Dox) of 500 ng/ml doxycycline. (B) DN-SREBP-1c prevented apoptosis. DNA fragmentation was assessed in DN-SREBP-1c^*23 cells cultured in 30 mM glucose medium for 0, 24, 48, and 72 hours, in the presence (+Dox) or absence (-Dox) of 500 ng/ml doxycycline. (C) DN-SREBP-1c partially restored glucose-stimulated insulin secretion. DN-SREBP-1c^*23 cells in 24-well dishes were cultured in either standard (11.2 mM; Control) or 30 mM glucose (High Glucose) medium for 48 hours. After 5 hours equilibration in 2.5 mM glucose medium, cells were washed twice with KRBH. Insulin release from DN-SREBP-1c^*23 cells stimulated with either 2.5 (Basal) or 20 mM glucose was determined by radio-immunoassay and expressed as a percentage of cellular insulin content. Data represent mean ± s.e.m. of six independent experiments. ^*P<0.01; ^**P<0.001.