We have previously identified a parasite‐derived peptide, FhHDM‐1, that prevented the progression of diabetes in nonobese diabetic (NOD) mice. Disease prevention was mediated by the activation of the PI3K/Akt pathway to promote β ‐cell survival and metabolism without inducing proliferation. To determine the molecular mechanisms driving the antidiabetogenic effects of FhHDM‐1, miRNA:mRNA interactions and in silico predictions of the gene networks were characterised in β ‐cells, which were exposed to the proinflammatory cytokines that mediate β ‐cell destruction in Type 1 diabetes (T1D), in the presence and absence of FhHDM‐1. The predicted gene targets of miRNAs differentially regulated by FhHDM‐1 mapped to the biological pathways that regulate β ‐cell biology. Six miRNAs were identified as important nodes in the regulation of PI3K/Akt signaling. Additionally, IGF‐2 was identified as a miRNA gene target that mediated the beneficial effects of FhHDM‐1 on β ‐cells. The findings provide a putative mechanism by which FhHDM‐1 positively impacts β ‐cells to permanently prevent diabetes. As β ‐cell death/dysfunction underlies diabetes development, FhHDM‐1 opens new therapeutic avenues.

The Parasite‐Derived Peptide, FhHDM‐1, Selectively Modulates miRNA Expression in <i>β</i>‐Cells to Prevent Apoptotic Pathways Induced by Proinflammatory Cytokines

The Parasite‐Derived Peptide, FhHDM‐1, Selectively Modulates miRNA Expression in β‐Cells to Prevent Apoptotic Pathways Induced by Proinflammatory Cytokines