The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes
Open accessAbstract
Type 1 diabetes (T1D) is an autoimmune disease characterized by insulitis and islet β-cell loss. Thus, an effective therapy may require β-cell restoration and immune suppression. Currently, there is no treatment that can achieve both goals efficiently. We report here that GABA exerts antidiabetic effects by acting on both the islet β-cells and immune system. Unlike in adult brain or islet α-cells in which GABA exerts hyperpolarizing effects, in islet β-cells, GABA produces membrane depolarization and Ca 2+influx, leading to the activation of PI3-K/Akt–dependent growth and survival pathways. This provides a potential mechanism underlying our in vivo findings that GABA therapy preserves β-cell mass and prevents the development of T1D. Remarkably, in severely diabetic mice, GABA restores β-cell mass and reverses the disease. Furthermore, GABA suppresses insulitis and systemic inflammatory cytokine production. The β-cell regenerative and immunoinhibitory effects of GABA provide insights into the role of GABA in regulating islet cell function and glucose homeostasis, which may find clinical application.
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Cites
The biology of incretin hormones
Drucker, D. J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.004 · Cited by 2,210
Type 1 diabetes: new perspectives on disease pathogenesis and treatment
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Is there more to gaba than synaptic inhibition?
Owens, D. F., & Kriegstein, A. R. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn919 · Cited by 1,156
The role of inflammation in insulitis and β-cell loss in type 1 diabetes
Eizirik, D. L., Colli, M. L., & Ortis, F. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.21 · Cited by 1,011
Inhibitory role for GABA in autoimmune inflammation
Bhat, R., Axtell, R., Mitra, A., Miranda, M., Lock, C., Tsien, R. W., & Steinman, L. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0915139107 · Cited by 509
Immune cell crosstalk in type 1 diabetes
Lehuen, A., Diana, J., Zaccone, P., & Cooke, A. (2010) · Nature Reviews Immunology · doi:10.1038/nri2787 · Cited by 476
Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels
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Trophic actions of GABA on neuronal development
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Self-citationSpontaneous Autoimmune Diabetes in Monoclonal T Cell Nonobese Diabetic Mice
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Cited by
Gut microbiota, obesity and diabetes
Patterson, E., Ryan, P. M., Cryan, J. F., Dinan, T. G., Ross, R. P., Fitzgerald, G. F., & Stanton, C. (2016) · Postgraduate Medical Journal · doi:10.1136/postgradmedj-2015-133285 · Cited by 552
Long-Term GABA Administration Induces Alpha Cell-Mediated Beta-like Cell Neogenesis
Ben-Othman, N., Vieira, A., Courtney, M., Record, F., Gjernes, E., Avolio, F., Hadzic, B., Druelle, N., Napolitano, T., Navarro-Sanz, S., et al. (2017) · Cell · doi:10.1016/j.cell.2016.11.002 · Cited by 322
GABA is an effective immunomodulatory molecule
Jin, Z., Mendu, S. K., & Birnir, B. (2013) · Amino Acids · doi:10.1007/s00726-011-1193-7 · Cited by 289
Microbes, immunity, and behavior: psychoneuroimmunology meets the microbiome
Dinan, T. G., & Cryan, J. F. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.103 · Cited by 246
GABA Promotes Human β-Cell Proliferation and Modulates Glucose Homeostasis
Purwana, I., Zheng, J., Li, X., Deurloo, M., Son, D. O., Zhang, Z., Liang, C., Shen, E., Tadkase, A., Feng, Z.-P., et al. (2014) · Diabetes · doi:10.2337/db14-0153 · Cited by 183
Self-citation
Metadata
- Authors
- Soltani, N., Qiu, H., Aleksic, M., Glinka, Y., Zhao, F., Liu, R., Li, Y., Zhang, N., Chakrabarti, R., Ng, T., Jin, T., Zhang, H., Lu, W.-Y., Feng, Z.-P., Prud'homme, G. J., & Wang, Q.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2011-06-27
- Volume
- 108
- Issue
- 28
- Pages
- 11692-11697
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2050397606
- Cited by
- 417
- References
- 47
- FWCI
- 20.79
- Type
- journal article
- Language
- en
- Open access
- green
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- Soltani, N., Qiu, H., Aleksic, M., Glinka, Y., Zhao, F., Liu, R., Li, Y., Zhang, N., Chakrabarti, R., Ng, T., Jin, T., Zhang, H., Lu, W.-Y., Feng, Z.-P., Prud'homme, G. J., & Wang, Q. (2011). GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1102715108
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