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

Abstract

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.