{"id":3886,"date":"2025-02-19T11:44:24","date_gmt":"2025-02-19T10:44:24","guid":{"rendered":"https:\/\/www.ub.edu\/ibub\/?p=3886"},"modified":"2025-02-19T11:54:02","modified_gmt":"2025-02-19T10:54:02","slug":"researchers-describe-new-molecular-mechanisms-linked-to-insulin-resistance","status":"publish","type":"post","link":"https:\/\/www.ub.edu\/ibub\/researchers-describe-new-molecular-mechanisms-linked-to-insulin-resistance\/","title":{"rendered":"Researchers describe new molecular mechanisms linked to insulin resistance"},"content":{"rendered":"\n<p><strong>Insulin resistance precedes and predicts the onset of type 2 diabetes mellitus (DM2), a chronic disease that causes high morbidity and mortality worldwide. In affected people, insulin is unable to facilitate the uptake of glucose through tissues and organs, leading to an increase in blood glucose (chronic hyperglycaemia). Since skeletal muscle is the tissue that uses the most glucose in response to insulin action, it is the most affected tissue by insulin resistance.<\/strong><\/p>\n\n\n\n<p>Now, a study published in <em><a href=\"https:\/\/biosignaling.biomedcentral.com\/articles\/10.1186\/s12964-024-01972-5\">Cell Communication and Signaling <\/a><\/em>describes new molecular mechanisms to understand insulin resistance in skeletal muscle and to outline future drug targets for DM2.<br><br>The study is led by Manuel V\u00e1zquez-Carrera, from the UB\u2019s Faculty of Pharmacy and Food Sciences, the Institute of Biomedicine of the UB (IBUB) and the Sant Joan de D\u00e9u Research Institute (IRSJD) and the Networking Biomedical Research Centre\u2019s Diabetes and Associated Metabolic Diseases area (CIBERDEM). Ricardo Rodr\u00edguez-Calvo (CIBERDEM and Universitat Rovira i Virgili), Antoni Camins (UBNeuro and CIBERNED) and Walter Wahli, from the University of Lausanne (Switzerland), among other experts, also signed the paper.<br><br><strong>Exploring the role of the insulin receptor<\/strong><br>\u200b\u200b\u200b\u200b\u200b\u200b\u200b<br>Poorly controlled diabetes is a serious global health problem that can damage patients\u2019 blood vessels, heart, eyes, kidneys and other organs.<\/p>\n\n\n\n<p><em>Studies have shown that during the development of insulin resistance, many steps in the metabolic pathway activated by insulin are altered. However, much less attention has so far been paid to what happens to the insulin receptor.<\/em><\/p>\n\n\n\n<p>Professor Manuel V\u00e1zquez-Carrera notes that \u201cthe insulin signalling pathway is initiated when insulin binds to a receptor on the cells of insulin-responsive tissues. This receptor is composed of the \u03b1-subunit of the insulin receptor (InsR\u03b1) and the \u03b2-subunit (InsR\u03b2)\u201d. \u201cInsulin binding to InsR\u03b1 derepresses the tyrosine kinase activity of the \u03b2-subunit (InsR\u03b2). This initiates a whole metabolic pathway with different steps that eventually allow glucose transporters to translocate from the interior to the cell membrane to allow glucose to enter\u201d, he continues.<br><br>The study assesses whether peroxisome proliferator-activated receptor (PPAR) \u03b2\/\u03b4 can regulate InsR\u03b2 levels in mouse muscle and myotubes in culture. \u201cThe results show that deletion of the <em>PPAR\u03b2\/\u03b4 <\/em>gene in mice reduces InsR\u03b2 protein levels in skeletal muscle compared to non-genetically modified mice. GW501516 \u2014 a PPAR\u03b2\/\u03b4 agonist \u2014 has also been shown to increase InsR\u03b2 protein levels in mice muscle\u201d, says V\u00e1zquez-Carrera.<br><br>The expert adds that \u201cthe reduction of InsR\u03b2 levels in cultured myotubes caused by an activator of endoplasmic reticulum stress \u2014 a process involved in the development of insulin resistance and DM2 \u2014 is partially reversed when cells are incubated in the presence of this PPAR\u03b2\/\u03b4 agonist\u201d. \u201cSpecifically, this agonist also decreased reticulum stress and lysosomal activity, the latter of which is responsible for degrading the InsR\u03b2 protein, which could explain the beneficial effect of this compound on the levels of this protein\u201d, he says.<br><br>The results also reveal how protein levels of ephrin receptor tyrosine kinase B4 (EphB4) \u2014 a factor that binds to InsR\u03b2 and facilitates its endocytosis and degradation in lysosomes \u2014 were increased in skeletal muscle from PPAR\u03b2\/\u03b4-deficient mice. However, the PPAR\u03b2\/\u03b4 agonist decreased levels in skeletal muscle from non-genetically modified mice.<br>\u200b\u200b\u200b\u200b\u200b\u200b\u200b<br>The results of this study identify new mechanisms by which PPAR\u03b2\/\u03b4 regulates InsR\u03b2 protein levels in skeletal muscle. \u201cThe research describes new actions of this nuclear receptor that may help explain its beneficial effects on insulin resistance and DM2\u201d, concludes V\u00e1zquez-Carrera.<\/p>\n\n\n\n<p><strong>Reference article:<\/strong><br><br>\u200b\u200b\u200b\u200b\u200b\u200b\u200bWang, Jue-Rui; Jurado-Aguilar, Javier; Barroso, Emma; Rodr\u00edguez-Calvo, Ricardo; Camins, Antoni; Wahli, Xalter; Palomer, Xavier; V\u00e1zquez-Carrera, Manuel.<a href=\"https:\/\/biosignaling.biomedcentral.com\/articles\/10.1186\/s12964-024-01972-5\"> \u00abPPAR\u03b2\/\u03b4 upregulates the insulin receptor \u03b2 subunit in skeletal muscle by reducing lysosomal activity and EphB4 levels\u00bb.<\/a><em> Cell Communication and Signaling<\/em>, December 2024. DOI: 10.1186\/s12964-024-01972-5<\/p>\n\n\n\n<p>UB New <a href=\"https:\/\/web.ub.edu\/en\/web\/actualitat\/w\/mechanisms-insulin-resistance?referer=noticies\">[+]<\/a><\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n","protected":false},"excerpt":{"rendered":"<p>Insulin resistance precedes and predicts the onset of type 2 diabetes mellitus (DM2), a chronic disease that causes high morbidity and mortality worldwide. In affected people, insulin is unable to facilitate the uptake of glucose through tissues and organs, leading to an increase in blood glucose (chronic hyperglycaemia). Since skeletal muscle is the tissue that &#8230; <a title=\"Researchers describe new molecular mechanisms linked to insulin resistance\" class=\"read-more\" href=\"https:\/\/www.ub.edu\/ibub\/researchers-describe-new-molecular-mechanisms-linked-to-insulin-resistance\/\" aria-label=\"More on Researchers describe new molecular mechanisms linked to insulin resistance\">Read more<\/a><\/p>\n","protected":false},"author":4,"featured_media":3890,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[3],"tags":[131,19,135,136,129,132,133,134,42],"class_list":["post-3886","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-development","tag-ibub","tag-insulin-receptor","tag-insulin-resistance","tag-insuline","tag-metabolic","tag-pathway","tag-receptor","tag-research"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v24.5 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Researchers describe new molecular mechanisms linked to insulin resistance - IBUB - Institut de Biomedicina de la Universitat de Barcelona<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.ub.edu\/ibub\/researchers-describe-new-molecular-mechanisms-linked-to-insulin-resistance\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Researchers describe new molecular mechanisms linked to insulin resistance - IBUB - Institut de Biomedicina de la Universitat de Barcelona\" \/>\n<meta property=\"og:description\" content=\"Insulin resistance precedes and predicts the onset of type 2 diabetes mellitus (DM2), a chronic disease that causes high morbidity and mortality worldwide. In affected people, insulin is unable to facilitate the uptake of glucose through tissues and organs, leading to an increase in blood glucose (chronic hyperglycaemia). Since skeletal muscle is the tissue that ... 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