{"entity": "researcher", "timestamp": "2026-08-20T20:36:21.670Z", "family": "Welsh", "given": "Nils", "initials": "N", "orcid": "0000-0001-5926-5407", "affiliations": ["Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. nils.welsh@mcb.uu.se."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/a128a9534c854b5194f3d4b93087db4f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/a128a9534c854b5194f3d4b93087db4f"}}, "publications": [{"entity": "publication", "iuid": "0932ca69e65249dd8c52b5ad8d0f7f16", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0932ca69e65249dd8c52b5ad8d0f7f16.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0932ca69e65249dd8c52b5ad8d0f7f16"}}, "title": "Imatinib protects against human beta-cell death via inhibition of mitochondrial respiration and activation of AMPK.", "authors": [{"family": "Elksnis", "given": "Andris", "initials": "A"}, {"family": "Schiffer", "given": "Tomas A", "initials": "TA"}, {"family": "Palm", "given": "Fredrik", "initials": "F"}, {"family": "Wang", "given": "Yun", "initials": "Y"}, {"family": "Cen", "given": "Jing", "initials": "J"}, {"family": "Turpaev", "given": "Kyril", "initials": "K"}, {"family": "Ngamjariyawat", "given": "Anongnad", "initials": "A"}, {"family": "Younis", "given": "Shady", "initials": "S"}, {"family": "Huang", "given": "Suling", "initials": "S"}, {"family": "Shen", "given": "Yu", "initials": "Y"}, {"family": "Leng", "given": "Ying", "initials": "Y"}, {"family": "Bergsten", "given": "Peter", "initials": "P"}, {"family": "Karlsborn", "given": "Tony", "initials": "T"}, {"family": "Welsh", "given": "Nils", "initials": "N", "orcid": "0000-0001-5926-5407", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a128a9534c854b5194f3d4b93087db4f.json"}}, {"family": "Wang", "given": "Xuan", "initials": "X"}], "type": "journal article", "published": "2021-10-14", "journal": {"title": "Clin. Sci.", "issn": "1470-8736", "volume": "135", "issue": "19", "pages": "2243-2263", "issn-l": "0143-5221"}, "abstract": "The protein tyrosine kinase inhibitor imatinib is used in the treatment of various malignancies but may also promote beneficial effects in the treatment of diabetes. The aim of the present investigation was to characterize the mechanisms by which imatinib protects insulin producing cells. Treatment of non-obese diabetic (NOD) mice with imatinib resulted in increased beta-cell AMP-activated kinase (AMPK) phosphorylation. Imatinib activated AMPK also in vitro, resulting in decreased ribosomal protein S6 phosphorylation and protection against islet amyloid polypeptide (IAPP)-aggregation, thioredoxin interacting protein (TXNIP) up-regulation and beta-cell death. 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) mimicked and compound C counteracted the effect of imatinib on beta-cell survival. Imatinib-induced AMPK activation was preceded by reduced glucose/pyruvate-dependent respiration, increased glycolysis rates, and a lowered ATP/AMP ratio. Imatinib augmented the fractional oxidation of fatty acids/malate, possibly via a direct interaction with the beta-oxidation enzyme enoyl coenzyme A hydratase, short chain, 1, mitochondrial (ECHS1). In non-beta cells, imatinib reduced respiratory chain complex I and II-mediated respiration and acyl-CoA carboxylase (ACC) phosphorylation, suggesting that mitochondrial effects of imatinib are not beta-cell specific. In conclusion, tyrosine kinase inhibitors modestly inhibit mitochondrial respiration, leading to AMPK activation and TXNIP down-regulation, which in turn protects against beta-cell death.", "doi": "10.1042/CS20210604", "pmid": "34569605", "labels": [], "xrefs": [{"db": "pii", "key": "229850"}], "notes": [], "created": "2026-08-20T09:28:28.446Z", "modified": "2026-08-20T09:28:28.469Z"}, {"entity": "publication", "iuid": "3a08411ff5834c6a87b03cdcf6222ff5", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3a08411ff5834c6a87b03cdcf6222ff5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3a08411ff5834c6a87b03cdcf6222ff5"}}, "title": "ZBED6 counteracts high-fat diet-induced glucose intolerance by maintaining beta cell area and reducing excess mitochondrial activation.", "authors": [{"family": "Wang", "given": "Xuan", "initials": "X", "orcid": "0000-0002-6672-017X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ff425a1ecee4680932e8b626533e528.json"}}, {"family": "Younis", "given": "Shady", "initials": "S", "orcid": "0000-0002-4319-1738", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cd2c4773dcf84b9eb1b82d19e5e2039c.json"}}, {"family": "Cen", "given": "Jing", "initials": "J"}, {"family": "Wang", "given": "Yun", "initials": "Y"}, {"family": "Krizhanovskii", "given": "Camilla", "initials": "C"}, {"family": "Andersson", "given": "Leif", "initials": "L", "orcid": "0000-0002-4085-6968", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7c8202937eda401fa0d07f583589359d.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": "2021-10-00", "journal": {"title": "Diabetologia", "issn": "1432-0428", "volume": "64", "issue": "10", "pages": "2292-2305", "issn-l": "0012-186X"}, "abstract": "ZBED6 (zinc finger, BED-type containing 6) is known to regulate muscle mass by suppression of Igf2 gene transcription. In insulin-producing cell lines, ZBED6 maintains proliferative capacity at the expense of differentiation and beta cell function. The aim was to study the impact of Zbed6 knockout on beta cell function and glucose tolerance in C57BL/6 mice.\n\nBeta cell area and proliferation were determined in Zbed6 knockout mice using immunohistochemical analysis. Muscle and fat distribution were assessed using micro-computed tomography. Islet gene expression was assessed by RNA sequencing. Effects of a high-fat diet were analysed by glucose tolerance and insulin tolerance tests. ZBED6 was overexpressed in EndoC-\u03b2H1 cells and human islet cells using an adenoviral vector. Beta cell cell-cycle analysis, insulin release and mitochondrial function were studied in vitro using propidium iodide staining and flow cytometry, ELISA, the Seahorse technique, and the fluorescent probes JC-1 and MitoSox.\n\nIslets from Zbed6 knockout mice showed lowered expression of the cell cycle gene Pttg1, decreased beta cell proliferation and decreased beta cell area, which occurred independently from ZBED6 effects on Igf2 gene expression. Zbed6 knockout mice, but not wild-type mice, developed glucose intolerance when given a high-fat diet. The high-fat diet Zbed6 knockout islets displayed upregulated expression of oxidative phosphorylation genes and genes associated with beta cell differentiation. In vitro, ZBED6 overexpression resulted in increased EndoC-\u03b2H1 cell proliferation and a reduced glucose-stimulated insulin release in human islets. ZBED6 also reduced mitochondrial JC-1 J-aggregate formation, mitochondrial oxygen consumption rates (OCR) and mitochondrial reactive oxygen species (ROS) production, both at basal and palmitate + high glucose-stimulated conditions. ZBED6-induced inhibition of OCR was not rescued by IGF2 addition. ZBED6 reduced levels of the mitochondrial regulator PPAR-\u03b3 related coactivator 1 protein (PRC) and bound its promoter/enhancer region. Knockdown of PRC resulted in a lowered OCR.\n\nIt is concluded that ZBED6 is required for normal beta cell replication and also limits excessive beta cell mitochondrial activation in response to an increased functional demand. ZBED6 may act, at least in part, by restricting PRC-mediated mitochondrial activation/ROS production, which may lead to protection against beta cell dysfunction and glucose intolerance in vivo.", "doi": "10.1007/s00125-021-05517-0", "pmid": "34296320", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8423654"}, {"db": "pii", "key": "10.1007/s00125-021-05517-0"}], "notes": [], "created": "2026-08-20T06:38:52.849Z", "modified": "2026-08-20T06:38:52.964Z"}]}