To efficiently cluster hPSC-derived pancreatic progenitors into 3D structures, scientists discovered 10 chemicals that not only retained the pancreatic progenitors in 3D clusters but also enhanced their potentiality towards NKX6.1+/INS+β cells.
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To search other possible mechanisms, scientists found the mRNA level and protein level of MKP7 (a phosphatase for phospho-JNK) were dramatically reduced in pancreatic β cells in the islets from NR4A1 knockout mice compared with that from wild type mice.
[Cell Death & Disease]
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Pu, Z., Yu, T., Liu, D., Jin, C., Sadiq, E., Qiao, X., Li, X., Chen, Y., Zhang, J., Tian, M., Li, S., Zhao, R., & Wang, X. (2021). NR4A1 enhances MKP7 expression to diminish JNK activation induced by ROS or ER-stress in pancreatic β cells for surviving. Cell Death Discovery, 7(1), 1–13. https://doi.org/10.1038/s41420-021-00521-0 Cite
Min6 cells were induced by 5 mg/dl UA and the cell proliferation, apoptosis, and insulin release were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and glucose-stimulated insulin secretion, respectively.
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Reserachers described and validated the use of the SUnSET approach to demonstrate through FACS and Western Blot that glucose increases protein translation in the human cell line EndoC-βH2
[Journal of Biological Chemistry]
Scientists review emerging evidence that developmental and homeostatic regulation of β-cell function involves collaboration between lineage-determining and signal-dependent transcription factors.
[Trends in Endocrinology and Metabolism]
The authors review recent advances in the fields of pancreas development and lineage reprogramming.
[Current Opinion in Genetics & Development]
Researchers used phasor – Fluorescence Lifetime Imaging Microscopy to monitor oxidative phosphorylation and glycolysis in living islet cells before and after glucose stimulation.
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Wang, Z., Gurlo, T., Matveyenko, A. V., Elashoff, D., Wang, P., Rosenberger, M., Junge, J. A., Stevens, R. C., White, K. L., Fraser, S. E., & Butler, P. C. (2021). Live-cell imaging of glucose-induced metabolic coupling of β and α cell metabolism in health and type 2 diabetes. Communications Biology, 4(1), 1–11. https://doi.org/10.1038/s42003-021-02113-1 Cite
Single-cell transcriptomic analyses of mouse β cells demonstrate that HG-9-91-01 induces a wave of activating transcription factor (ATF)6-dependent unfolded protein response (UPR) before cell cycle entry.
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Charbord, J., Ren, L., Sharma, R. B., Johansson, A., Ågren, R., Chu, L., Tworus, D., Schulz, N., Charbord, P., Stewart, A. F., Wang, P., Alonso, L. C., & Andersson, O. (2021). In vivo screen identifies a SIK inhibitor that induces β cell proliferation through a transient UPR. Nature Metabolism, 3(5), 682–700. https://doi.org/10.1038/s42255-021-00391-x Cite
Researchers examined the unique molecular players underlying each distinct form of autophagy in β-cells, including selective autophagy of mitochondria, insulin granules, lipid, intracellular amyloid aggregates, endoplasmic reticulum, and peroxisomes.
The aims are not to discuss specificities of pathways controlling secretion but to compare qualitative and quantitative features of glucose-induced insulin secretion in isolated human islets and in living human subjects.
Researchers found that the SARS-CoV-2 receptor, ACE2 and related entry factors were expressed in β-cells, with selectively high expression of NRP1.
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Wu, C.-T., Lidsky, P. V., Xiao, Y., Lee, I. T., Cheng, R., Nakayama, T., Jiang, S., Demeter, J., Bevacqua, R. J., Chang, C. A., Whitener, R. L., Stalder, A. K., Zhu, B., Chen, H., Goltsev, Y., Tzankov, A., Nayak, J. V., Nolan, G. P., Matter, M. S., … Jackson, P. K. (2021). SARS-CoV-2 infects human pancreatic β-cells and elicits β-cell impairment. Cell Metabolism, 0(0). https://doi.org/10.1016/j.cmet.2021.05.013 Cite