Pancreatic Progenitor Epigenome Maps Prioritize Type 2 Diabetes Risk Genes with Roles in Development

The authors investigated contributions of regulatory programs active during pancreatic development to type 2 diabetes risk.
[eLife]
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Amylin Deposition Activates HIF1α and 6-Phosphofructo-2-Kinase/Fructose-2, 6-Biphosphatase 3 (PFKFB3) Signaling in Failing Hearts of Non-Human Primates

Researchers demonstrated that in non-human primates, amylin deposition in heart failure contributed to cardiac dysfunction via activation of HIF1α and PFKFB3 signaling.
[Communications Biology]
Liu, M., Li, N., Qu, C., Gao, Y., Wu, L., & Hu, L. G. (2021). Amylin deposition activates HIF1α and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) signaling in failing hearts of non-human primates. Communications Biology, 4(1), 1–17. https://doi.org/10.1038/s42003-021-01676-3 Cite
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Obesity-Induced Inflammation: The Impact of the Hematopoietic Stem Cell Niche

The authors explore the role of the multicellular hematopoietic stem cell niche in hematopoiesis and inflammation, and the potential contribution of this niche to the hematopoietic response to obesity.
[JCI Insight]
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Chromatin 3D Interaction Analysis of the STARD10 Locus Unveils FCHSD2 as a Regulator of Insulin Secretion

Using chromatin conformation capture, investigators showed that an enhancer cluster in the STARD10 type 2 diabetes locus forms a defined 3D chromatin domain.
[Cell Reports]
Hu, M., Cebola, I., Carrat, G., Jiang, S., Nawaz, S., Khamis, A., Canouil, M., Froguel, P., Schulte, A., Solimena, M., Ibberson, M., Marchetti, P., Cardenas-Diaz, F. L., Gadue, P. J., Hastoy, B., Alemeida-Souza, L., McMahon, H., & Rutter, G. A. (2021). Chromatin 3D interaction analysis of the STARD10 locus unveils FCHSD2 as a regulator of insulin secretion. Cell Reports, 34(5). https://doi.org/10.1016/j.celrep.2021.108703 Cite
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Oramed Doses Patients Across Multiple Sites in Phase III Oral Insulin Study

Oramed Pharmaceuticals, Inc. announced that randomization of patients in its first Phase III study of its oral insulin capsule ORMD-0801 for the treatment of type 2 diabetes was under way.
[Oramed Pharmaceuticals, Inc.]
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Long Non-Coding RNAs (lncRNAs) in Cardiovascular Disease Complication of Type 2 Diabetes

The authors discuss the roles of lncRNAs in type 2 diabetes (T2D) and cardiovascular disease (CVD) conditions and their diagnostic potential as molecular biomarkers for CVD complications in T2D.
[Diagnostics]
Ismail, N., Abdullah, N., Abdul Murad, N. A., Jamal, R., & Sulaiman, S. A. (2021). Long Non-Coding RNAs (lncRNAs) in Cardiovascular Disease Complication of Type 2 Diabetes. Diagnostics, 11(1), 145. https://doi.org/10.3390/diagnostics11010145 Cite
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TMEM16A Channel Upregulation in Arterial Smooth Muscle Cells Produces Vasoconstriction during Diabetes

Investigators tested the hypothesis that TMEM16A, a calcium-activated chloride channel, contributed to modifications in arterial contractility during type 2 diabetes (T2D). They indicated that T2D increased TMEM16A mRNA in arterial smooth muscle cells and total and surface TMEM16A protein in resistance-size arteries of mice.
[American Journal of Physiology-Heart and Circulatory Physiology]
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Mitophagy Protects Beta Cells from Inflammatory Damage in Diabetes

Mitophagy-deficient β-cells were sensitized to inflammatory stress, leading to the accumulation of fragmented dysfunctional mitochondria, increased β-cell death, and hyperglycemia.
[JCI Insight]
Sidarala, V., Pearson, G. L., Parekh, V. S., Thompson, B., Christen, L., Gingerich, M. A., Zhu, J., Stromer, T., Ren, J., Reck, E. C., Chai, B., Corbett, J. A., Mandrup-Poulsen, T., Satin, L. S., & Soleimanpour, S. A. (2020). Mitophagy protects beta cells from inflammatory damage in diabetes. JCI Insight. https://doi.org/10.1172/jci.insight.141138 Cite
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Oramed Initiates Phase III Trial of Oral Insulin

Oramed Pharmaceuticals, Inc. announced it has screened the first patients in its global Phase III trials of its oral insulin capsule ORMD-0801 for the treatment of type 2 diabetes. The patients were screened at US sites participating in Oramed’s ORA-D-013-1 trial, one of two Phase III trials being conducted in accordance with FDA approved protocols.
[Oramed Pharmaceuticals, Inc.]
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Genetic Variant Effects on Gene Expression in Human Pancreatic Islets and Their Implications for T2D

The authors explored the relationship between genetic variants influencing predisposition to type 2 diabetes and related glycemic traits, and human pancreatic islet transcription using data from 420 donors.
[Nature Communications]
Viñuela, A., Varshney, A., van de Bunt, M., Prasad, R. B., Asplund, O., Bennett, A., Boehnke, M., Brown, A. A., Erdos, M. R., Fadista, J., Hansson, O., Hatem, G., Howald, C., Iyengar, A. K., Johnson, P., Krus, U., MacDonald, P. E., Mahajan, A., Manning Fox, J. E., … McCarthy, M. I. (2020). Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D. Nature Communications, 11(1), 4912. https://doi.org/10.1038/s41467-020-18581-8 Cite
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Dysfunction of CD8+ PD-1+ T Cells in Type 2 Diabetes Caused by the Impairment of Metabolism-Immune Axis

In CD8+ splenic T cells from the HFS mice, glycolysis/basal respiration ratio was significantly reduced and reversed by metformin.
[Scientific Reports]
Nojima, I., Eikawa, S., Tomonobu, N., Hada, Y., Kajitani, N., Teshigawara, S., Miyamoto, S., Tone, A., Uchida, H. A., Nakatsuka, A., Eguchi, J., Shikata, K., Udono, H., & Wada, J. (2020). Dysfunction of CD8 + PD-1 + T cells in type 2 diabetes caused by the impairment of metabolism-immune axis. Scientific Reports, 10(1), 14928. https://doi.org/10.1038/s41598-020-71946-3 Cite
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