Fig. 4. The presenilin-1 established ER Ca²⁺ leak is essential for a proper biphasic insulin secretion upon elevated glucose in pancreatic β-cells. (A) GSIS is shown as insulin secretion rate in β-cells (INS-1). Lines and points represent insulin secretion rate under control conditions (Ctrl; black) and knock-down of presenilin-1 (β-cells; red). (B) Cumulative total concentration of secreted insulin at the indicated time points from β-cells (INS-1) calculated in ng/ml either under control conditions (black) or knock-down of presenilin-1 (INS-1; red). To equilibrate the insulin secretion, cells were kept on HBSS buffer containing 3 mM glucose for 30 min. Afterwards medium was changed to HBSS buffer containing 16 mM glucose and medium was sampled at the indicated time points. (C) Total insulin content in β-cells (INS-1) transfected with siRNA control (Ctrl) or siRNA against presenilin-1 (siPS1). *p<0.05 versus control using the unpaired Student's t-test (n=5).