Obesity-induced adipocytes promote diabetes mellitus by regulating β islet cell function through exosome miR-138-5p
Abstract Insulin dysfunction can lead to type 1 diabetes mellitus (T1DM), inducing an increase in blood glucose levels. Unfortunately, there remains a need for more effective clinical treatments for DM. Obesity is closely associated with islet dysfunction, but these inside mechanisms remain unclear....
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-01564-4 |
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| author | Shihong Fan Nengjuan Li |
| author_facet | Shihong Fan Nengjuan Li |
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| description | Abstract Insulin dysfunction can lead to type 1 diabetes mellitus (T1DM), inducing an increase in blood glucose levels. Unfortunately, there remains a need for more effective clinical treatments for DM. Obesity is closely associated with islet dysfunction, but these inside mechanisms remain unclear. We indicated that obesity-induced adipocytes inhibit insulin secretion (IS) from β islet cells (β-cells) by elevating the expression of their exosome miR-138-5p. Our study proved the high expression of miR-138-5p in exosomes isolated from the fat tissue of obese mice, as well as in exosomes derived from obesity-induced 3T3-L1 cells. The underlying mechanism possibly involves the upregulation of miR-138-5p which suppressed IS while increasing apoptosis in MIN6 cells. miR-138-5p knockdown upregulated insulin production and decreased apoptosis in MIN6 cells. Moreover, dual-luciferase reporter assays revealed the direct regulating effects of miR-138-5p on SOX4. Moreover, SOX4 expression affects the abundance of proteins involved in the Wnt/β-catenin pathway. Under obesity conditions, miR-138-5p in adipocyte exosomes affects IS and ultimately β-cell function by regulating the SOX4-mediated Wnt/β-catenin pathway in β cells. These results not only presented new insights into the interaction between obesity and T1DM but also provide new possible therapeutic mechanisms for obesity-related T1DM. |
| format | Article |
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| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-ef48c15751274bf1b8d83c1917faeb5c2025-08-20T02:34:02ZengNature PortfolioScientific Reports2045-23222025-05-0115111210.1038/s41598-025-01564-4Obesity-induced adipocytes promote diabetes mellitus by regulating β islet cell function through exosome miR-138-5pShihong Fan0Nengjuan Li1Department of Endocrinology, Ningbo Medical Center Lihuili HospitalDepartment of Endocrinology, The Second Affiliated Hospital of Zhejiang Chinese Medical UniversityAbstract Insulin dysfunction can lead to type 1 diabetes mellitus (T1DM), inducing an increase in blood glucose levels. Unfortunately, there remains a need for more effective clinical treatments for DM. Obesity is closely associated with islet dysfunction, but these inside mechanisms remain unclear. We indicated that obesity-induced adipocytes inhibit insulin secretion (IS) from β islet cells (β-cells) by elevating the expression of their exosome miR-138-5p. Our study proved the high expression of miR-138-5p in exosomes isolated from the fat tissue of obese mice, as well as in exosomes derived from obesity-induced 3T3-L1 cells. The underlying mechanism possibly involves the upregulation of miR-138-5p which suppressed IS while increasing apoptosis in MIN6 cells. miR-138-5p knockdown upregulated insulin production and decreased apoptosis in MIN6 cells. Moreover, dual-luciferase reporter assays revealed the direct regulating effects of miR-138-5p on SOX4. Moreover, SOX4 expression affects the abundance of proteins involved in the Wnt/β-catenin pathway. Under obesity conditions, miR-138-5p in adipocyte exosomes affects IS and ultimately β-cell function by regulating the SOX4-mediated Wnt/β-catenin pathway in β cells. These results not only presented new insights into the interaction between obesity and T1DM but also provide new possible therapeutic mechanisms for obesity-related T1DM.https://doi.org/10.1038/s41598-025-01564-4Diabetes mellitusObesityExosomeβ islet cellmiR-138-5pSOX4 |
| spellingShingle | Shihong Fan Nengjuan Li Obesity-induced adipocytes promote diabetes mellitus by regulating β islet cell function through exosome miR-138-5p Scientific Reports Diabetes mellitus Obesity Exosome β islet cell miR-138-5p SOX4 |
| title | Obesity-induced adipocytes promote diabetes mellitus by regulating β islet cell function through exosome miR-138-5p |
| title_full | Obesity-induced adipocytes promote diabetes mellitus by regulating β islet cell function through exosome miR-138-5p |
| title_fullStr | Obesity-induced adipocytes promote diabetes mellitus by regulating β islet cell function through exosome miR-138-5p |
| title_full_unstemmed | Obesity-induced adipocytes promote diabetes mellitus by regulating β islet cell function through exosome miR-138-5p |
| title_short | Obesity-induced adipocytes promote diabetes mellitus by regulating β islet cell function through exosome miR-138-5p |
| title_sort | obesity induced adipocytes promote diabetes mellitus by regulating β islet cell function through exosome mir 138 5p |
| topic | Diabetes mellitus Obesity Exosome β islet cell miR-138-5p SOX4 |
| url | https://doi.org/10.1038/s41598-025-01564-4 |
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