The authors identified KMT2D as a potent tumor suppressor in melanoma through an in vivo epigenome-focused pooled RNAi screen and confirmed the finding by using a genetically engineered mouse model based on conditional and melanocyte-specific deletion of KMT2D.
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Maitituoheti, M., Keung, E. Z., Tang, M., Yan, L., Alam, H., Han, G., Singh, A. K., Raman, A. T., Terranova, C., Sarkar, S., Orouji, E., Amin, S. B., Sharma, S., Williams, M., Samant, N. S., Dhamdhere, M., Zheng, N., Shah, T., Shah, A., … Rai, K. (2020). Enhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma. Cell Reports, 33(3). https://doi.org/10.1016/j.celrep.2020.108293 Cite
Scientists systematically compared zinc and insulin contents in the permanent INS-1E and BRIN-BD11 β-cells and in the native rat pancreatic islets by flow cytometry, confocal microscopy, immunoblotting, specific messenger RNA and total insulin analysis.
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Dzianová, P., Asai, S., Chrudinová, M., Kosinová, L., Potalitsyn, P., Šácha, P., Hadravová, R., Selicharová, I., Kříž, J., Turkenburg, J. P., Brzozowski, A. M., Jiráček, J., & Žáková, L. (n.d.). The efficiency of insulin production and its content in insulin-expressing model β-cells correlate with their Zn2+ levels. Open Biology, 10(10), 200137. https://doi.org/10.1098/rsob.200137 Cite
The authors present the AMP-activated protein kinase (AMPK) role in eukaryotic cells and focus on the relationship between AMPK activity and the regulation of BER system through its main component—8-oxoguanine glycosylase
[Molecular Biology Reports]
Researchers showed that SPARC enhanced the promoting effect of Muscarinic receptor agonist oxotremorine-M on insulin secretion in cultured mouse islets. Overexpression of SPARC down-regulated RGS4, a negative regulator of β-cell M3 muscarinic receptors.
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In a series of gain-of-function and loss-of-function experiments in rodent and human myotubes, researchers demonstrated that BNIP3L accumulation triggers mitochondrial depolarization, calcium-dependent activation of DNM1L/DRP1, and mitophagy.
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Rosa, S. C. da S., Martens, M. D., Field, J. T., Nguyen, L., Kereliuk, S. M., Hai, Y., Chapman, D., Diehl-Jones, W., Aliani, M., West, A. R., Thliveris, J., Ghavami, S., Rampitsch, C., Dolinsky, V. W., & Gordon, J. W. (2020). BNIP3L/Nix-induced mitochondrial fission, mitophagy, and impaired myocyte glucose uptake are abrogated by PRKA/PKA phosphorylation. Autophagy, 0(0), 1–16. https://doi.org/10.1080/15548627.2020.1821548 Cite
Scientists found a consistent, abnormal methylation pattern in insulinomas. They found that abnormal insulin (INS) promoter methylation and altered transcription factor expression created alternative drivers of INS expression, replacing canonical PDX1-driven beta cell specification with a pathological, looping, distal enhancer-based form of transcriptional regulation.
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Researchers demonstrated that somatostatin and glucagon secretion were linked in a reciprocal feedback cycle with somatostatin inhibiting glucagon secretion at low and high glucose levels, and glucagon stimulating somatostatin secretion via the glucagon and GLP-1 receptors.
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Plasma glucagon responses during hyperinsulinemic-hypoglycemic clamps (40 mg/dL) were assessed in dogs with spontaneous diabetes (n=13) and healthy non-diabetic dogs (n=6). Plasma C-peptide responses to intravenous glucagon were measured to assess endogenous insulin secretion. Plasma pancreatic polypeptide, epinephrine and norepinephrine were measured as indices of parasympathetic and sympathoadrenal autonomic responses to insulin-induced hypoglycemia.
[American Journal of Physiology-Endocrinology and Metabolism]
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Scientists report that leptin augments NMDA subtype of glutamate receptors function via Src kinase-mediated phosphorylation of the GluN2A subunit.
[Journal of Biological Chemistry]
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Scientists highlight the development of in vitro cell culture models that allow systematic studies of pancreatic cell mechanobiology in response to extracellular matrix proteins, biomechanical effects, soluble factor modulation of biomechanics, substrate stiffness, fluid flow and topography.
[Frontiers in Bioengineering and Biotechnology]
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Researchers investigated the effect of Tankyrase inhibition in osteoblast differentiation of human skeletal MSCs.
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Almasoud, N., Binhamdan, S., Younis, G., Alaskar, H., Alotaibi, A., Manikandan, M., Alfayez, M., Kassem, M., & AlMuraikhi, N. (2020). Tankyrase inhibitor XAV-939 enhances osteoblastogenesis and mineralization of human skeletal (mesenchymal) stem cells. Scientific Reports, 10(1), 16746. https://doi.org/10.1038/s41598-020-73439-9 Cite