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 |
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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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| author | Inah Camaya Meredith Hill Dayna Sais Nham Tran Bronwyn O’Brien Sheila Donnelly |
| author_facet | Inah Camaya Meredith Hill Dayna Sais Nham Tran Bronwyn O’Brien Sheila Donnelly |
| author_sort | Inah Camaya |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7e4cbdf429684d70a6f99154e5f1a893 |
| institution | DOAJ |
| issn | 2314-6753 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-7e4cbdf429684d70a6f99154e5f1a8932025-08-20T03:06:55ZengWileyJournal of Diabetes Research2314-67532024-01-01202410.1155/2024/8555211The Parasite-Derived Peptide, FhHDM-1, Selectively Modulates miRNA Expression in β-Cells to Prevent Apoptotic Pathways Induced by Proinflammatory CytokinesInah Camaya0Meredith Hill1Dayna Sais2Nham Tran3Bronwyn O’Brien4Sheila Donnelly5The School of Life SciencesSchool of Biomedical EngineeringSchool of Biomedical EngineeringSchool of Biomedical EngineeringThe School of Life SciencesThe School of Life SciencesWe 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.http://dx.doi.org/10.1155/2024/8555211 |
| spellingShingle | Inah Camaya Meredith Hill Dayna Sais Nham Tran Bronwyn O’Brien Sheila Donnelly The Parasite-Derived Peptide, FhHDM-1, Selectively Modulates miRNA Expression in β-Cells to Prevent Apoptotic Pathways Induced by Proinflammatory Cytokines Journal of Diabetes Research |
| title | The Parasite-Derived Peptide, FhHDM-1, Selectively Modulates miRNA Expression in β-Cells to Prevent Apoptotic Pathways Induced by Proinflammatory Cytokines |
| title_full | The Parasite-Derived Peptide, FhHDM-1, Selectively Modulates miRNA Expression in β-Cells to Prevent Apoptotic Pathways Induced by Proinflammatory Cytokines |
| title_fullStr | The Parasite-Derived Peptide, FhHDM-1, Selectively Modulates miRNA Expression in β-Cells to Prevent Apoptotic Pathways Induced by Proinflammatory Cytokines |
| title_full_unstemmed | The Parasite-Derived Peptide, FhHDM-1, Selectively Modulates miRNA Expression in β-Cells to Prevent Apoptotic Pathways Induced by Proinflammatory Cytokines |
| title_short | The Parasite-Derived Peptide, FhHDM-1, Selectively Modulates miRNA Expression in β-Cells to Prevent Apoptotic Pathways Induced by Proinflammatory Cytokines |
| title_sort | parasite derived peptide fhhdm 1 selectively modulates mirna expression in β cells to prevent apoptotic pathways induced by proinflammatory cytokines |
| url | http://dx.doi.org/10.1155/2024/8555211 |
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