Intermolecular network involved in calcium-dependent apoptosis of pancreatic beta-cells and possible targets for diabetes treatment

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We investigated mechanisms for apoptosis induction in pancreatic beta-cells, which can be responsible for impairment of insulin secretion in type 2 diabetes. The treatment of beta-cell line INS-1 with H_2O_2, which resembled diabetic oxidative stress, induced a transient intracellular Ca^<2+> elevation. The response was mediated by Ca^<2+> release from the endoplasmic reticulum through IP3 receptors and terminated within one hour. This seemed to become a trigger signal for beta-cell apoptosis induction ; the transient cytosolic Ca^<2+> elevation led to prolonged elevation of mitochondrial Ca^<2+> concentration, thereby inducing cytochrome c release from mitochondria and beta-cell apoptosis.