We have engineered a peptide containing the CDGSH domain of CISD2, critical for its interaction with IP3R. Overexpression of our CISD2 peptide or treatment with its cell-penetrating peptide (CPP)-conjugated form restores calcium homeostasis in WFS1- or CISD2-deficient cells, and overexpressing the homologous dCISD peptide suppresses diabetes-like phenotypes in WS model flies. This evidence concerns the gene CISD2 and diabetes mellitus.