Version 1
: Received: 26 August 2024 / Approved: 27 August 2024 / Online: 27 August 2024 (18:40:19 CEST)
How to cite:
Ha, S. E.; Singh, R.; Jin, B.; Baek, G.; Jorgensen, B. G.; Zogg, H.; Debnath, S.; Park, H. S.; Cho, H.; Watkins, C. M.; Cho, S.; Kim, M.-S.; Lee, M. Y.; Yu, T. Y.; Jeong, J. W.; Ro, S. miR-10a/b-5p-NCOR2 Regulates Insulin-Resistant Diabetes in Female Mice. Preprints2024, 2024081944. https://doi.org/10.20944/preprints202408.1944.v1
Ha, S. E.; Singh, R.; Jin, B.; Baek, G.; Jorgensen, B. G.; Zogg, H.; Debnath, S.; Park, H. S.; Cho, H.; Watkins, C. M.; Cho, S.; Kim, M.-S.; Lee, M. Y.; Yu, T. Y.; Jeong, J. W.; Ro, S. miR-10a/b-5p-NCOR2 Regulates Insulin-Resistant Diabetes in Female Mice. Preprints 2024, 2024081944. https://doi.org/10.20944/preprints202408.1944.v1
Ha, S. E.; Singh, R.; Jin, B.; Baek, G.; Jorgensen, B. G.; Zogg, H.; Debnath, S.; Park, H. S.; Cho, H.; Watkins, C. M.; Cho, S.; Kim, M.-S.; Lee, M. Y.; Yu, T. Y.; Jeong, J. W.; Ro, S. miR-10a/b-5p-NCOR2 Regulates Insulin-Resistant Diabetes in Female Mice. Preprints2024, 2024081944. https://doi.org/10.20944/preprints202408.1944.v1
APA Style
Ha, S. E., Singh, R., Jin, B., Baek, G., Jorgensen, B. G., Zogg, H., Debnath, S., Park, H. S., Cho, H., Watkins, C. M., Cho, S., Kim, M. S., Lee, M. Y., Yu, T. Y., Jeong, J. W., & Ro, S. (2024). miR-10a/b-5p-NCOR2 Regulates Insulin-Resistant Diabetes in Female Mice. Preprints. https://doi.org/10.20944/preprints202408.1944.v1
Chicago/Turabian Style
Ha, S. E., Jin Woo Jeong and Seungil Ro. 2024 "miR-10a/b-5p-NCOR2 Regulates Insulin-Resistant Diabetes in Female Mice" Preprints. https://doi.org/10.20944/preprints202408.1944.v1
Abstract
Gender and biological sex have distinct impacts on the pathogenesis of type 2 diabetes (T2D). Estrogen deficiency is known to predispose female mice to T2D. In our previous study, we found that high-fat, high-sucrose diet (HFHSD) induces T2D in male mice through the miR-10b-5p/KLF11/KIT pathway, but not in females, highlighting hormonal disparities in T2D susceptibility. However, the underlying molecular mechanisms of this hormonal protection in females remain elusive. To address this knowledge gap, we utilized ovariectomized, estrogen-deficient female mice, fed them a HFHSD to induce T2D, and investigated the molecular mechanisms pathway in estrogen-deficient diabetic female mice, cell lines, and patients with T2D in female. Initially, female mice fed a HFHSD exhibited delayed onset of T2D, but ovariectomy-induced estrogen deficiency promptly precipitated T2D without delay. Intriguingly, insulin (INS) was upregulated, while insulin receptor (INSR) and protein kinase B (AKT) were downregulated in these estrogen-deficient diabetic female mice, indicating insulin-resistant T2D. These dysregulations of INS, INSR, and AKT were mediated by a miR-10a/b-5p-NCOR2 axis. Treatment of miR-10a/b-5p effectively alleviated hyperglycemia in estrogen-deficient T2D female mice, while β-estradiol temporarily reduced hyperglycemia. Consistent with the murine findings, plasma samples from female T2D patients exhibited significant reductions in miR-10a/b-5p, estrogen, and INSR, but increased insulin levels. Our findings suggest that estrogen protect against insulin-resistant T2D in females through miR-10a/b-5p/NCOR2 pathway, indicating the potential therapeutic benefits of miR-10a/b-5p restoration in female T2D management.
Biology and Life Sciences, Endocrinology and Metabolism
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
