{"entity": "researcher", "timestamp": "2026-08-23T09:27:08.769Z", "family": "Cen", "given": "Jing", "initials": "J", "orcid": "0000-0001-6014-3984", "affiliations": ["Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, SE-751 23 Uppsala, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/fab963f027504b1cb41e73af56d86d74.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/fab963f027504b1cb41e73af56d86d74"}}, "publications": [{"entity": "publication", "iuid": "34a857d3b0a04e34b5b23f929b758de6", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/34a857d3b0a04e34b5b23f929b758de6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/34a857d3b0a04e34b5b23f929b758de6"}}, "title": "GDF15 Protects Insulin-Producing Beta Cells against Pro-Inflammatory Cytokines and Metabolic Stress via Increased Deamination of Intracellular Adenosine.", "authors": [{"family": "Ngamjariyawat", "given": "Anongnad", "initials": "A"}, {"family": "Cen", "given": "Jing", "initials": "J", "orcid": "0000-0001-6014-3984", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fab963f027504b1cb41e73af56d86d74.json"}}, {"family": "Wang", "given": "Xuan", "initials": "X", "orcid": "0000-0002-6672-017X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ff425a1ecee4680932e8b626533e528.json"}}, {"family": "Welsh", "given": "Nils", "initials": "N", "orcid": "0000-0001-5926-5407", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a128a9534c854b5194f3d4b93087db4f.json"}}], "type": "journal article", "published": "2024-01-08", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "25", "issue": "2", "issn-l": null}, "abstract": "It has been proposed that antidiabetic drugs, such as metformin and imatinib, at least in part, promote improved glucose tolerance in type 2 diabetic patients via increased production of the inflammatory cytokine GDF15. This is supported by studies, performed in rodent cell lines and mouse models, in which the addition or production of GDF15 improved beta-cell function and survival. The aim of the present study was to determine whether human beta cells produce GDF15 in response to antidiabetic drugs and, if so, to further elucidate the mechanisms by which GDF15 modulates the function and survival of such cells. The effects and expression of GDF15 were analyzed in human insulin-producing EndoC-betaH1 cells and human islets. We observed that alpha and beta cells exhibit considerable heterogeneity in GDF15 immuno-positivity. The predominant form of GDF15 present in islet and EndoC-betaH1 cells was pro-GDF15. Imatinib, but not metformin, increased pro-GDF15 levels in EndoC-betaH1 cells. Under basal conditions, exogenous GDF15 increased human islet oxygen consumption rates. In EndoC-betaH1 cells and human islets, exogenous GDF15 partially ameliorated cytokine- or palmitate + high-glucose-induced loss of function and viability. GDF15-induced cell survival was paralleled by increased inosine levels, suggesting a more efficient disposal of intracellular adenosine. Knockdown of adenosine deaminase, the enzyme that converts adenosine to inosine, resulted in lowered inosine levels and loss of protection against cytokine- or palmitate + high-glucose-induced cell death. It is concluded that imatinib-induced GDF15 production may protect human beta cells partially against inflammatory and metabolic stress. Furthermore, it is possible that the GDF15-mediated activation of adenosine deaminase and the increased disposal of intracellular adenosine participate in protection against beta-cell death.", "doi": "10.3390/ijms25020801", "pmid": "38255875", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10815691"}, {"db": "pii", "key": "ijms25020801"}], "notes": [], "created": "2026-08-21T13:03:51.063Z", "modified": "2026-08-21T13:03:51.137Z"}, {"entity": "publication", "iuid": "e0d4f4a849a04b6ab1a59fc67c09bdbc", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e0d4f4a849a04b6ab1a59fc67c09bdbc.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e0d4f4a849a04b6ab1a59fc67c09bdbc"}}, "title": "Pharmacological Inhibition of NOX4 Improves Mitochondrial Function and Survival in Human Beta-Cells.", "authors": [{"family": "Elksnis", "given": "Andris", "initials": "A", "orcid": "0000-0003-0353-326X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ad831360d5ac4fe9baf1edaad46173e7.json"}}, {"family": "Cen", "given": "Jing", "initials": "J", "orcid": "0000-0001-6014-3984", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fab963f027504b1cb41e73af56d86d74.json"}}, {"family": "Wikstr\u00f6m", "given": "Per", "initials": "P"}, {"family": "Carlsson", "given": "Per-Ola", "initials": "PO"}, {"family": "Welsh", "given": "Nils", "initials": "N", "orcid": "0000-0001-5926-5407", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a128a9534c854b5194f3d4b93087db4f.json"}}], "type": "journal article", "published": "2021-12-08", "journal": {"title": "Biomedicines", "issn": "2227-9059", "volume": "9", "issue": "12", "issn-l": null}, "abstract": "Previous studies have reported beneficial effects of NADPH oxidase 4 (NOX4) inhibition on beta-cell survival in vitro and in vivo. The mechanisms by which NOX4 inhibition protects insulin producing cells are, however, not known. The aim of the present study was to investigate the effects of a pharmacological NOX4 inhibitor (GLX7013114) on human islet and EndoC-\u03b2H1 cell mitochondrial function, and to correlate such effects with survival in islets of different size, activity, and glucose-stimulated insulin release responsiveness. We found that maximal oxygen consumption rates, but not the rates of acidification and proton leak, were increased in islets after acute NOX4 inhibition. In EndoC-\u03b2H1 cells, NOX4 inhibition increased the mitochondrial membrane potential, as estimated by JC-1 fluorescence; mitochondrial reactive oxygen species (ROS) production, as estimated by MitoSOX fluorescence; and the ATP/ADP ratio, as assessed by a bioluminescent assay. Moreover, the insulin release from EndoC-\u03b2H1 cells at a high glucose concentration increased with NOX4 inhibition. These findings were paralleled by NOX4 inhibition-induced protection against human islet cell death when challenged with high glucose and sodium palmitate. The NOX4 inhibitor protected equally well islets of different size, activity, and glucose responsiveness. We conclude that pharmacological alleviation of NOX4-induced inhibition of beta-cell mitochondria leads to increased, and not decreased, mitochondrial ROS, and this was associated with protection against cell death occurring in different types of heterogeneous islets. Thus, NOX4 inhibition or modulation may be a therapeutic strategy in type 2 diabetes that targets all types of islets.", "doi": "10.3390/biomedicines9121865", "pmid": "34944680", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8698703"}, {"db": "pii", "key": "biomedicines9121865"}], "notes": [], "created": "2026-08-21T13:01:20.636Z", "modified": "2026-08-21T13:01:20.758Z"}]}