The Parasite-Derived Peptide, FhHDM-1, Selectively Modulates miRNA Expression in β-Cells to Prevent Apoptotic Pathways Induced by Proinflammatory Cytokines
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 determ...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2024/8555211 |
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| Summary: | 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. |
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| ISSN: | 2314-6753 |