The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells
Open accessAbstract
OBJECTIVE—MicroRNAs are short, noncoding RNAs that regulate gene expression. We hypothesized that the phosphatidylinositol 3-kinase (PI 3-kinase) cascade known to be important in β-cell physiology could be regulated by microRNAs. Here, we focused on the pancreas-specific miR-375 as a potential regulator of its predicted target 3′-phosphoinositide–dependent protein kinase-1 (PDK1), and we analyzed its implication in the response of insulin-producing cells to elevation of glucose levels. RESEARCH DESIGN AND METHODS—We used insulinoma-1E cells to analyze the effects of miR-375 on PDK1 protein level and downstream signaling using Western blotting, glucose-induced insulin gene expression using quantitative RT-PCR, and DNA synthesis by measuring thymidine incorporation. Moreover, we analyzed the effect of glucose on miR-375 expression in both INS-1E cells and primary rat islets. Finally, miR-375 expression in isolated islets was analyzed in diabetic Goto-Kakizaki (GK) rats. RESULTS—We found that miR-375 directly targets PDK1 and reduces its protein level, resulting in decreased glucose-stimulatory action on insulin gene expression and DNA synthesis. Furthermore, glucose leads to a decrease in miR-375 precursor level and a concomitant increase in PDK1 protein. Importantly, regulation of miR-375 expression by glucose occurs in primary rat islets as well. Finally, miR-375 expression was found to be decreased in fed diabetic GK rat islets. CONCLUSIONS—Our findings provide evidence for a role of a pancreatic-specific microRNA, miR-375, in the regulation of PDK1, a key molecule in PI 3-kinase signaling in pancreatic β-cells. The effects of glucose on miR-375 are compatible with the idea that miR-375 is involved in glucose regulation of insulin gene expression and β-cell growth.
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Cites
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miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting
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MicroRNA-124a Regulates Foxa2 Expression and Intracellular Signaling in Pancreatic β-Cell Lines*
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Self-citation
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Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice
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Rottiers, V., & Näär, A. M. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3313 · Cited by 1,156
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Interplay between miRNAs and human diseases
Paul, P., Chakraborty, A., Sarkar, D., Langthasa, M., Rahman, M., Bari, M., Singha, R. S., Malakar, A. K., & Chakraborty, S. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.25854 · Cited by 420
Metadata
- Authors
- El Ouaamari, A., Baroukh, N., Martens, G. A., Lebrun, P., Pipeleers, D., & van Obberghen, E.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2008-10-01
- Volume
- 57
- Issue
- 10
- Pages
- 2708-2717
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2151428158
- Cited by
- 430
- References
- 10
- FWCI
- 18.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
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