Enhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma

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.
[Cell Reports]
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
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The Efficiency of Insulin Production and Its Content in Insulin-Expressing Model β-Cells Correlate with Their Zn2+ Levels

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.
[Open Biology]
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
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The Role of AMPK in Metabolism and Its Influence on DNA Damage Repair

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]
Szewczuk, M., Boguszewska, K., Kaźmierczak-Barańska, J., & Karwowski, B. T. (2020). The role of AMPK in metabolism and its influence on DNA damage repair. Molecular Biology Reports. https://doi.org/10.1007/s11033-020-05900-x Cite
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SPARC Promotes Insulin Secretion through Down-Regulation of RGS4 Protein in Pancreatic β Cells

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.
[Scientific Reports]
Hu, L., He, F., Huang, M., Zhao, Q., Cheng, L., Said, N., Zhou, Z., Liu, F., & Dai, Y.-S. (2020). SPARC promotes insulin secretion through down-regulation of RGS4 protein in pancreatic β cells. Scientific Reports, 10(1), 17581. https://doi.org/10.1038/s41598-020-74593-w Cite
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BNIP3L/Nix-Induced Mitochondrial Fission, Mitophagy, and Impaired Myocyte Glucose Uptake Are Abrogated by PRKA/PKA Phosphorylation

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.
[Autophagy]
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
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Aberrant Methylation Underlies Insulin Gene Expression in Human Insulinoma

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.
[Nature Communications]
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Paracrine Regulation of Somatostatin Secretion by Insulin and Glucagon in Mouse Pancreatic Islets

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.
[Diabetologia]
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Co-impairment of Autonomic and Glucagon Responses to Insulin-Induced Hypoglycemia in Dogs with Naturally-Occurring Insulin-Dependent Diabetes Mellitus

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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Leptin Modulates Pancreatic β-Cell Membrane Potential through Src Kinase-Mediated Phosphorylation of NMDA Receptors

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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Developmentally-Inspired Biomimetic Culture Models to Produce Functional Islet-Like Cells From Pluripotent Precursors

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]
Tran, R., Moraes, C., & Hoesli, C. A. (2020). Developmentally-Inspired Biomimetic Culture Models to Produce Functional Islet-Like Cells From Pluripotent Precursors. Frontiers in Bioengineering and Biotechnology, 8. https://doi.org/10.3389/fbioe.2020.583970 Cite
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Tankyrase Inhibitor XAV-939 Enhances Osteoblastogenesis and Mineralization of Human Skeletal (Mesenchymal) Stem Cells

Researchers investigated the effect of Tankyrase inhibition in osteoblast differentiation of human skeletal MSCs.
[Scientific Reports]
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
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