{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T15:01:10Z","timestamp":1781622070047,"version":"3.54.5"},"reference-count":47,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:p>\n                    Starch\u2010binding domain\u2010containing protein 1 (Stbd1) is a glycogen\u2010binding protein which localizes to the endoplasmic reticulum (ER) membrane and ER\u2010mitochondria contact sites (ERMCs). The protein undergoes\n                    <jats:italic>N<\/jats:italic>\n                    \u2010myristoylation, which is a major determinant of its subcellular targeting. Stbd1 has been implicated in the control of glucose homeostasis, as evidenced by the finding that mice with targeted inactivation of\n                    <jats:italic>Stbd1<\/jats:italic>\n                    display insulin resistance associated with increased ERMCs in the liver. In the present study, we addressed the effects of increased\n                    <jats:italic>Stbd1<\/jats:italic>\n                    expression levels on insulin signaling. We show that\n                    <jats:italic>Stbd1<\/jats:italic>\n                    overexpression enhances cellular sensitivity to insulin and improves insulin resistance in an\n                    <jats:italic>in vitro<\/jats:italic>\n                    hepatocyte cell model. We further demonstrate that increased\n                    <jats:italic>Stbd1<\/jats:italic>\n                    expression levels are associated with enhanced activation of the AMP\u2010activated protein kinase (AMPK), which is a central regulator of metabolism and an attractive therapeutic target for metabolic disorders related to insulin resistance, such as type 2 diabetes (T2D). The activation of AMPK signaling and the improved cellular response to insulin induced by\n                    <jats:italic>Stbd1<\/jats:italic>\n                    overexpression occurred independently of\n                    <jats:italic>N<\/jats:italic>\n                    \u2010myristoylation and associated changes in the number of ERMCs, glycogen levels, mitochondrial calcium, mitochondrial morphology, and respiratory function. Collectively, our findings uncover a new level of interaction between Stbd1 and AMPK, with Stbd1 acting as an upstream activator of AMPK signaling. Given that first\u2010line drug treatments for insulin resistance and T2D are known activators of the AMPK pathway, these findings may provide a new perspective for the development of more effective therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1111\/febs.70040","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T22:46:28Z","timestamp":1741733188000},"page":"2882-2901","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Stbd1 stimulates\n                    <scp>AMPK<\/scp>\n                    signaling and alleviates insulin resistance in an\n                    <i>in vitro<\/i>\n                    hepatocyte model"],"prefix":"10.1111","volume":"292","author":[{"given":"Andria","family":"Theodoulou","sequence":"first","affiliation":[{"name":"Biochemical Genetics Department The Cyprus Institute of Neurology and Genetics  Nicosia Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thilo","family":"Speckmann","sequence":"additional","affiliation":[{"name":"Department of Experimental Diabetology German Institute of Human Nutrition  Potsdam\u2010Rehbruecke Germany"},{"name":"German Center for Diabetes Research (DZD)  M\u00fcnchen\u2010Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louiza","family":"Potamiti","sequence":"additional","affiliation":[{"name":"Cancer Genetics, Therapeutics and Ultrastructural Pathology Department The Cyprus Institute of Neurology and Genetics  Nicosia Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otto","family":"Baba","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Anatomy Tokushima University Graduate School  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Morita","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Anatomy Tokushima University Graduate School  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthi","family":"Drousiotou","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Department The Cyprus Institute of Neurology and Genetics  Nicosia Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1450-3552","authenticated-orcid":false,"given":"Mihalis I.","family":"Panayiotidis","sequence":"additional","affiliation":[{"name":"Cancer Genetics, Therapeutics and Ultrastructural Pathology Department The Cyprus Institute of Neurology and Genetics  Nicosia Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Sch\u00fcrmann","sequence":"additional","affiliation":[{"name":"Department of Experimental Diabetology German Institute of Human Nutrition  Potsdam\u2010Rehbruecke Germany"},{"name":"German Center for Diabetes Research (DZD)  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