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Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells.
Nat Commun
January 2025
Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.
View Article and Find Full Text PDFUltrafast multicellular calcium imaging of calcium spikes in mouse beta cells in tissue slices.
Acta Physiol (Oxf)
February 2025
Faculty of Medicine, University of Maribor, Maribor, Slovenia.
Background: The crucial steps in beta cell stimulus-secretion coupling upon stimulation with glucose are oscillatory changes in metabolism, membrane potential, intracellular calcium concentration, and exocytosis. The changes in membrane potential consist of bursts of spikes, with silent phases between them being dominated by membrane repolarization and absence of spikes. Assessing intra- and intercellular coupling at the multicellular level is possible with ever-increasing detail, but our current ability to simultaneously resolve spikes from many beta cells remains limited to double-impalement electrophysiological recordings.
View Article and Find Full Text PDFFabrication of phospholipid polymer-modified alginate hydrogels for bioartificial pancreas.
J Biosci Bioeng
January 2025
Department of Chemical Systems Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan. Electronic address:
The bioartificial pancreas, composed of a semi-permeable hydrogel encapsulating insulin-secreting cells, has attracted attention as a treatment for type 1 diabetes. In this study, we developed phospholipid polymer-modified alginate hydrogel beads that encapsulated spheroids of the pancreatic beta cell line MIN6. The hydrogel beads were composed of methacrylated alginic acid, which enabled both ionic and covalent cross-linking, resulting in a hydrogel that was more stable than conventional alginate hydrogels.
View Article and Find Full Text PDFThe multifaceted function of FoxO1 in pancreatic β-cell dysfunction and insulin resistance: Therapeutic potential for type 2 diabetes.
Life Sci
January 2025
School of Life Science and Technology, Shandong Second Medical University, Weifang 261021, China. Electronic address:
The forkhead box O1 (FOXO1), the first discovered member of the FoxO family, is a critical transcription factor predominantly found in insulin-secreting and insulin-sensitive tissues. In the pancreas of adults, FoxO1 expression is restricted to islet β cells. We determined that in human islet microarray datasets, FoxO1 expression is higher than other FoxO transcription factors.
View Article and Find Full Text PDFThe Glucose-Lowering Effect of and D-Pinitol: Studies on Insulin Secretion in INS-1 Cells and the Reduction of Blood Glucose in Diabetic Rats.
Nutrients
January 2025
College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea.
Ice plant () is a vegetable with various therapeutic uses, one of which is its ability to prevent diabetes. The present study examined the insulin secretion effect related to the mechanism of action of ice plant extract (IPE) and its active compound D-pinitol in a rat insulin-secreting β-cell line, INS-1, as well as in diabetic rats. : The glucose-stimulated insulin secretion (GSIS) test and Western blotting were used to measure GSIS.
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