{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:27:21Z","timestamp":1789752441474,"version":"4.0.1"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100020098","name":"Innovative Health Initiative","doi-asserted-by":"publisher","award":["777460"],"award-info":[{"award-number":["777460"]}],"id":[{"id":"10.13039\/100020098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003092","name":"Diabetes Fonds","doi-asserted-by":"publisher","award":["2023.82.011"],"award-info":[{"award-number":["2023.82.011"]}],"id":[{"id":"10.13039\/501100003092","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/hypothesis<\/jats:title>\n                    <jats:p>Hypoglycaemia induces an acute and sustained inflammatory response both in people with type 1 diabetes and in people without diabetes. To investigate the role of adrenaline (epinephrine)\u00a0in this response, we measured the inflammatory effects of adrenaline in a concentration and timeframe comparable to that seen during hypoglycaemia, in people with type 1 diabetes and matched control participants without diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Adults with type 1 diabetes and matched control participants received adrenaline intravenously at 0.04 \u00b5g kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      min\n                      <jats:sup>\u22121<\/jats:sup>\n                      for 1 h. Blood was drawn at baseline, after 30, 60 and 180 min, and on days 1, 3 and 7 following start of adrenaline administration, to determine white blood cell counts, cytokine secretion using ex vivo stimulation of isolated monocytes and circulating inflammatory markers using the Olink inflammatory panel.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Adrenaline acutely increased neutrophil, lymphocyte and monocyte counts in both groups. While neutrophil and monocyte levels returned to baseline after 1 day, lymphocytes remained elevated for 7 days. Adrenaline acutely altered monocyte function towards a more inflammatory phenotype, reflected by increased secretion of cytokines after ex vivo stimulation with lipopolysaccharide in both groups. Adrenaline also increased circulating inflammatory proteins, including urokinase-type plasminogen activator, Fms-like tyrosine kinase 3 ligand, chemokine (C-X3-C motif) ligand 1 and fibroblast growth factor 21, after 7 days in both groups, with a more pronounced response in people with type 1 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>Levels of adrenaline similar to those seen in response to hypoglycaemia elicit an acute and prolonged inflammatory response in people with type 1 diabetes and matched control participants on a cellular, functional and protein level. These findings suggest that adrenaline is a prominent driver of inflammatory responses following hypoglycaemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT05990933<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-026-06667-9","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T21:41:41Z","timestamp":1769722901000},"page":"1675-1685","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Adrenaline is a prominent driver of inflammatory responses following hypoglycaemia"],"prefix":"10.1007","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8691-3633","authenticated-orcid":false,"given":"Ilyas F.","family":"Mustafajev","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3027-6369","authenticated-orcid":false,"given":"Marijn S.","family":"Hendriksz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6729-7193","authenticated-orcid":false,"given":"Rinke","family":"Stienstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0322-1653","authenticated-orcid":false,"given":"Cees J.","family":"Tack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1255-7741","authenticated-orcid":false,"given":"Bastiaan E.","family":"de Galan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5360-5439","authenticated-orcid":false,"given":"Rick I.","family":"Meijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"issue":"11","key":"6667_CR1","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.2337\/dci21-0043","volume":"44","author":"RIG Holt","year":"2021","unstructured":"Holt RIG, DeVries JH, Hess-Fischl A et al (2021) The management of type 1 diabetes in adults. A consensus report by the American diabetes association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 44(11):2589\u20132625. https:\/\/doi.org\/10.2337\/dci21-0043","journal-title":"Diabetes Care"},{"issue":"8","key":"6667_CR2","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1111\/dme.12878","volume":"33","author":"BM Frier","year":"2016","unstructured":"Frier BM, Jensen MM, Chubb BD (2016) Hypoglycaemia in adults with insulin-treated diabetes in the UK: self-reported frequency and effects. Diabet Med 33(8):1125\u20131132. https:\/\/doi.org\/10.1111\/dme.12878","journal-title":"Diabet Med"},{"issue":"6","key":"6667_CR3","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1002\/dmrr.482","volume":"20","author":"U Pedersen-Bjergaard","year":"2004","unstructured":"Pedersen-Bjergaard U, Pramming S, Heller SR et al (2004) Severe hypoglycaemia in 1076 adult patients with type 1 diabetes: influence of risk markers and selection. Diabetes Metab Res Rev 20(6):479\u2013486. https:\/\/doi.org\/10.1002\/dmrr.482","journal-title":"Diabetes Metab Res Rev"},{"key":"6667_CR4","doi-asserted-by":"publisher","first-page":"117158","DOI":"10.1016\/j.atherosclerosis.2023.06.005","volume":"394","author":"B Verges","year":"2024","unstructured":"Verges B (2024) Cardiovascular disease in type 1 diabetes, an underestimated danger: epidemiological and pathophysiological data. Atherosclerosis 394:117158. https:\/\/doi.org\/10.1016\/j.atherosclerosis.2023.06.005","journal-title":"Atherosclerosis"},{"issue":"2","key":"6667_CR5","doi-asserted-by":"publisher","first-page":"316","DOI":"10.2337\/dc14-0920","volume":"38","author":"K Khunti","year":"2015","unstructured":"Khunti K, Davies M, Majeed A, Thorsted BL, Wolden ML, Paul SK (2015) Hypoglycemia and risk of cardiovascular disease and all-cause mortality in insulin-treated people with type 1 and type 2 diabetes: a cohort study. Diabetes Care 38(2):316\u2013322. https:\/\/doi.org\/10.2337\/dc14-0920","journal-title":"Diabetes Care"},{"issue":"12","key":"6667_CR6","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1007\/s11883-024-01241-3","volume":"26","author":"A d'Aiello","year":"2024","unstructured":"d\u2019Aiello A, Filomia S, Brecciaroli M, Sanna T, Pedicino D, Liuzzo G (2024) Targeting inflammatory pathways in atherosclerosis: exploring new opportunities for treatment. Curr Atheroscler Rep 26(12):707\u2013719. https:\/\/doi.org\/10.1007\/s11883-024-01241-3","journal-title":"Curr Atheroscler Rep"},{"issue":"11","key":"6667_CR7","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1038\/s41419-024-07166-8","volume":"15","author":"A Ajoolabady","year":"2024","unstructured":"Ajoolabady A, Pratico D, Lin L et al (2024) Inflammation in atherosclerosis: pathophysiology and mechanisms. Cell Death Dis 15(11):817. https:\/\/doi.org\/10.1038\/s41419-024-07166-8","journal-title":"Cell Death Dis"},{"issue":"11","key":"6667_CR8","doi-asserted-by":"publisher","first-page":"3114","DOI":"10.1111\/dom.15205","volume":"25","author":"CEM Verhulst","year":"2023","unstructured":"Verhulst CEM, van Heck JIP, Fabricius TW et al (2023) Hypoglycaemia induces a sustained pro-inflammatory response in people with type 1 diabetes and healthy controls. Diabetes Obes Metab 25(11):3114\u20133124. https:\/\/doi.org\/10.1111\/dom.15205","journal-title":"Diabetes Obes Metab"},{"issue":"9","key":"6667_CR9","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1007\/s00125-018-4683-2","volume":"61","author":"JM Ratter","year":"2018","unstructured":"Ratter JM, Rooijackers HMM, Jacobs CWM, de Galan BE, Tack CJ, Stienstra R (2018) Hypoglycaemia induces recruitment of non-classical monocytes and cytotoxic lymphocyte subsets in type 1 diabetes. Diabetologia 61(9):2069\u20132071. https:\/\/doi.org\/10.1007\/s00125-018-4683-2","journal-title":"Diabetologia"},{"issue":"12","key":"6667_CR10","doi-asserted-by":"publisher","first-page":"2716","DOI":"10.2337\/db22-0246","volume":"71","author":"CEM Verhulst","year":"2022","unstructured":"Verhulst CEM, van Heck JIP, Fabricius TW et al (2022) Sustained proinflammatory effects of hypoglycemia in people with type 2 diabetes and in people without diabetes. Diabetes 71(12):2716\u20132727. https:\/\/doi.org\/10.2337\/db22-0246","journal-title":"Diabetes"},{"issue":"1","key":"6667_CR11","doi-asserted-by":"publisher","first-page":"503","DOI":"10.4049\/jimmunol.0902189","volume":"184","author":"S Dimitrov","year":"2010","unstructured":"Dimitrov S, Lange T, Born J (2010) Selective mobilization of cytotoxic leukocytes by epinephrine. J Immunol 184(1):503\u2013511. https:\/\/doi.org\/10.4049\/jimmunol.0902189","journal-title":"J Immunol"},{"key":"6667_CR12","doi-asserted-by":"publisher","first-page":"171","DOI":"10.3389\/fphar.2015.00171","volume":"6","author":"A Scanzano","year":"2015","unstructured":"Scanzano A, Cosentino M (2015) Adrenergic regulation of innate immunity: a review. Front Pharmacol 6:171. https:\/\/doi.org\/10.3389\/fphar.2015.00171","journal-title":"Front Pharmacol"},{"issue":"1","key":"6667_CR13","doi-asserted-by":"publisher","first-page":"93","DOI":"10.4049\/jimmunol.156.1.93","volume":"156","author":"M Schedlowski","year":"1996","unstructured":"Schedlowski M, Hosch W, Oberbeck R et al (1996) Catecholamines modulate human NK cell circulation and function via spleen-independent \u03b22-adrenergic mechanisms. J Immunol 156(1):93\u201399","journal-title":"J Immunol"},{"issue":"5","key":"6667_CR14","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1007\/BF00920243","volume":"13","author":"M Schedlowski","year":"1993","unstructured":"Schedlowski M, Falk A, Rohne A et al (1993) Catecholamines induce alterations of distribution and activity of human natural killer (NK) cells. J Clin Immunol 13(5):344\u2013351. https:\/\/doi.org\/10.1007\/BF00920243","journal-title":"J Clin Immunol"},{"issue":"4","key":"6667_CR15","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.2337\/db16-1091","volume":"66","author":"JM Ratter","year":"2017","unstructured":"Ratter JM, Rooijackers HM, Tack CJ et al (2017) Proinflammatory effects of hypoglycemia in humans with or without diabetes. Diabetes 66(4):1052\u20131061. https:\/\/doi.org\/10.2337\/db16-1091","journal-title":"Diabetes"},{"issue":"4","key":"6667_CR16","doi-asserted-by":"publisher","first-page":"e15042","DOI":"10.1111\/dme.15042","volume":"40","author":"N Ali","year":"2023","unstructured":"Ali N, El Hamdaoui S, Schouwenberg BJ, Tack CJ, de Galan BE (2023) Fall in prevalence of impaired awareness of hypoglycaemia in individuals with type 1 diabetes. Diabet Med 40(4):e15042. https:\/\/doi.org\/10.1111\/dme.15042","journal-title":"Diabet Med"},{"key":"6667_CR17","unstructured":"Holding O (2025) FAQ. Available from https:\/\/olink.com\/knowledge\/faq. Accessed 14 May 2025"},{"key":"6667_CR18","unstructured":"R Core Team (2024) R: a language and environment for statistical computing. Foundation for Statistical Computing, Vienna, Austria"},{"key":"6667_CR19","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: elegant graphics for data analysis","author":"H Wickham","year":"2016","unstructured":"Wickham H (2016) ggplot2: elegant graphics for data analysis. Springer-Verlag, New York"},{"issue":"2","key":"6667_CR20","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1161\/CIRCRESAHA.119.315800","volume":"127","author":"C van der Heijden","year":"2020","unstructured":"van der Heijden C, Groh L, Keating ST et al (2020) Catecholamines induce trained immunity in monocytes in vitro and in vivo. Circ Res 127(2):269\u2013283. https:\/\/doi.org\/10.1161\/CIRCRESAHA.119.315800","journal-title":"Circ Res"},{"issue":"4","key":"6667_CR21","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1096\/fasebj.10.4.8647351","volume":"10","author":"RJ Benschop","year":"1996","unstructured":"Benschop RJ, Jacobs R, Sommer B et al (1996) Modulation of the immunologic response to acute stress in humans by \u03b2-blockade or benzodiazepines. FASEB J 10(4):517\u2013524. https:\/\/doi.org\/10.1096\/fasebj.10.4.8647351","journal-title":"FASEB J"},{"key":"6667_CR22","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.bbi.2016.01.004","volume":"54","author":"MP Yeager","year":"2016","unstructured":"Yeager MP, Pioli PA, Collins J et al (2016) Glucocorticoids enhance the in vivo migratory response of human monocytes. Brain Behav Immun 54:86\u201394. https:\/\/doi.org\/10.1016\/j.bbi.2016.01.004","journal-title":"Brain Behav Immun"},{"issue":"1","key":"6667_CR23","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1093\/ejendo\/lvad076","volume":"189","author":"GA Ueland","year":"2023","unstructured":"Ueland GA, Methlie P, Heie A et al (2023) Substantial changes in inflammatory and cardiovascular biomarkers in patients with autonomous cortisol secretion. Eur J Endocrinol 189(1):78\u201386. https:\/\/doi.org\/10.1093\/ejendo\/lvad076","journal-title":"Eur J Endocrinol"},{"issue":"5","key":"6667_CR24","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1159\/000216188","volume":"16","author":"FS Dhabhar","year":"2009","unstructured":"Dhabhar FS (2009) Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. Neuroimmunomodulation 16(5):300\u2013317. https:\/\/doi.org\/10.1159\/000216188","journal-title":"Neuroimmunomodulation"},{"issue":"1","key":"6667_CR25","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1111\/j.1365-2362.1990.tb01790.x","volume":"20","author":"BM Fisher","year":"1990","unstructured":"Fisher BM, Hepburn DA, Smith JG, Frier BM (1990) The effect of \u03b1-adrenergic blockade on responses of peripheral blood cells to acute insulin-induced hypoglycaemia in humans. Eur J Clin Invest 20(1):51\u201355. https:\/\/doi.org\/10.1111\/j.1365-2362.1990.tb01790.x","journal-title":"Eur J Clin Invest"},{"issue":"2","key":"6667_CR26","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.imlet.2005.05.008","volume":"101","author":"K Mizuno","year":"2005","unstructured":"Mizuno K, Takahashi HK, Iwagaki H et al (2005) \u03b22-adrenergic receptor stimulation inhibits LPS-induced IL-18 and IL-12 production in monocytes. Immunol Lett 101(2):168\u2013172. https:\/\/doi.org\/10.1016\/j.imlet.2005.05.008","journal-title":"Immunol Lett"},{"issue":"2","key":"6667_CR27","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1097\/00000539-200302000-00040","volume":"96","author":"CY Li","year":"2003","unstructured":"Li CY, Chou TC, Lee CH, Tsai CS, Loh SH, Wong CS (2003) Adrenaline inhibits lipopolysaccharide-induced macrophage inflammatory protein-1\u03b1 in human monocytes: the role of \u03b2-adrenergic receptors. Anesth Analg 96(2):518\u2013523. https:\/\/doi.org\/10.1097\/00000539-200302000-00040","journal-title":"Anesth Analg"},{"key":"6667_CR28","doi-asserted-by":"publisher","first-page":"13886","DOI":"10.1038\/srep13886","volume":"5","author":"R Mukherjee","year":"2015","unstructured":"Mukherjee R, Kanti Barman P, Kumar Thatoi P, Tripathy R, Kumar Das B, Ravindran B (2015) Non-Classical monocytes display inflammatory features: Validation in Sepsis and Systemic Lupus Erythematous. Sci Rep 5:13886. https:\/\/doi.org\/10.1038\/srep13886","journal-title":"Sci Rep"},{"key":"6667_CR29","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.3389\/fimmu.2017.01061","volume":"8","author":"LE Lowry","year":"2017","unstructured":"Lowry LE, Zehring WA (2017) Potentiation of natural killer cells for cancer immunotherapy: a review of literature. Front Immunol 8:1061. https:\/\/doi.org\/10.3389\/fimmu.2017.01061","journal-title":"Front Immunol"},{"issue":"1","key":"6667_CR30","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s12933-023-02095-w","volume":"23","author":"CEM Verhulst","year":"2024","unstructured":"Verhulst CEM, van Heck JIP, Fabricius TW et al (2024) The impact of prior exposure to hypoglycaemia on the inflammatory response to a subsequent hypoglycaemic episode. Cardiovasc Diabetol 23(1):55. https:\/\/doi.org\/10.1186\/s12933-023-02095-w","journal-title":"Cardiovasc Diabetol"},{"key":"6667_CR31","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1080\/00365519009085799","volume":"201","author":"T Maki","year":"1990","unstructured":"Maki T, Kontula K, Harkonen M (1990) The beta-adrenergic system in man: physiological and pathophysiological response. Regulation of receptor density and functioning. Scand J Clin Lab Invest Suppl 201:25\u201343","journal-title":"Scand J Clin Lab Invest Suppl"},{"key":"6667_CR32","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/B978-0-12-411512-5.00017-8","volume":"68","author":"R Kvetnansky","year":"2013","unstructured":"Kvetnansky R, Lu X, Ziegler MG (2013) Stress-triggered changes in peripheral catecholaminergic systems. Adv Pharmacol 68:359\u2013397. https:\/\/doi.org\/10.1016\/B978-0-12-411512-5.00017-8","journal-title":"Adv Pharmacol"},{"issue":"4","key":"6667_CR33","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1055\/s-0044-1788296","volume":"33","author":"K Prasad","year":"2024","unstructured":"Prasad K (2024) Role of C-reactive protein, an inflammatory biomarker in the development of atherosclerosis and its treatment. Int J Angiol 33(4):271\u2013281. https:\/\/doi.org\/10.1055\/s-0044-1788296","journal-title":"Int J Angiol"},{"issue":"3","key":"6667_CR34","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.smim.2015.03.013","volume":"27","author":"J Viola","year":"2015","unstructured":"Viola J, Soehnlein O (2015) Atherosclerosis - A matter of unresolved inflammation. Semin Immunol 27(3):184\u2013193. https:\/\/doi.org\/10.1016\/j.smim.2015.03.013","journal-title":"Semin Immunol"},{"issue":"12","key":"6667_CR35","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","volume":"377","author":"PM Ridker","year":"2017","unstructured":"Ridker PM, Everett BM, Thuren T et al (2017) Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 377(12):1119\u20131131. https:\/\/doi.org\/10.1056\/NEJMoa1707914","journal-title":"N Engl J Med"},{"issue":"1","key":"6667_CR36","doi-asserted-by":"publisher","first-page":"27004","DOI":"10.31083\/FBL27004","volume":"30","author":"DP Vageli","year":"2025","unstructured":"Vageli DP, Doukas PG, Georgiou D et al (2025) HIF-1\u03b1 and VEGF immunophenotypes as potential biomarkers in the prognosis and evaluation of treatment efficacy of atherosclerosis: a systematic review of the literature. Front Biosci (Landmark Ed) 30(1):27004. https:\/\/doi.org\/10.31083\/FBL27004","journal-title":"Front Biosci (Landmark Ed)"},{"issue":"6","key":"6667_CR37","first-page":"884","volume":"58","author":"M Namiecinska","year":"2006","unstructured":"Namiecinska M, Wiktorowska-Owczarek A, Loboda A, Dulak J, Nowak JZ (2006) Cyclic AMP generating system in human microvascular endothelium is highly responsive to adrenaline. Pharmacol Rep 58(6):884\u2013889","journal-title":"Pharmacol Rep"},{"issue":"6","key":"6667_CR38","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1159\/000433540","volume":"24","author":"SN El-Zohairy","year":"2015","unstructured":"El-Zohairy SN, Oriowo MA, Ezeamuzie CI (2015) Cyclic adenosine monophosphate-mediated enhancement of vascular endothelial growth factor released by differentiated human monocytic cells: the role of protein kinase A. Med Princ Pract 24(6):548\u2013554. https:\/\/doi.org\/10.1159\/000433540","journal-title":"Med Princ Pract"},{"issue":"10","key":"6667_CR39","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1038\/aps.2013.92","volume":"34","author":"S Apostolakis","year":"2013","unstructured":"Apostolakis S, Spandidos D (2013) Chemokines and atherosclerosis: focus on the CX3CL1\/CX3CR1 pathway. Acta Pharmacol Sin 34(10):1251\u20131256. https:\/\/doi.org\/10.1038\/aps.2013.92","journal-title":"Acta Pharmacol Sin"},{"issue":"9","key":"6667_CR40","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.1253\/circj.cj-11-1457","volume":"76","author":"J Li","year":"2012","unstructured":"Li J, Guo Y, Luan X et al (2012) Independent roles of monocyte chemoattractant protein-1, regulated on activation, normal T-cell expressed and secreted and fractalkine in the vulnerability of coronary atherosclerotic plaques. Circ J 76(9):2167\u20132173. https:\/\/doi.org\/10.1253\/circj.cj-11-1457","journal-title":"Circ J"},{"issue":"1","key":"6667_CR41","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.atherosclerosis.2011.10.044","volume":"222","author":"B Fuhrman","year":"2012","unstructured":"Fuhrman B (2012) The urokinase system in the pathogenesis of atherosclerosis. Atherosclerosis 222(1):8\u201314. https:\/\/doi.org\/10.1016\/j.atherosclerosis.2011.10.044","journal-title":"Atherosclerosis"},{"key":"6667_CR42","doi-asserted-by":"publisher","first-page":"657881","DOI":"10.3389\/fphys.2021.657881","volume":"12","author":"A Golaszewska","year":"2021","unstructured":"Golaszewska A, Misztal T, Marcinczyk N, Chabielska E, Rusak T (2021) Adrenaline may contribute to prothrombotic condition via augmentation of platelet procoagulant response, enhancement of fibrin formation, and attenuation of fibrinolysis. Front Physiol 12:657881. https:\/\/doi.org\/10.3389\/fphys.2021.657881","journal-title":"Front Physiol"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-026-06667-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00125-026-06667-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-026-06667-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T11:08:06Z","timestamp":1777028886000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00125-026-06667-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,29]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["6667"],"URL":"https:\/\/doi.org\/10.1007\/s00125-026-06667-9","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,29]]},"assertion":[{"value":"12 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"We wholeheartedly thank all the volunteers for participating in this study. We would also like to thank E. Abbink, A. Rasing-Hoogveld, E. Lensen, M. Eybergen, E. Sanders, E. Otters-van Bodegom, K. Theijssen, S. Ahoud and C. Slaa (all Department Clinical Research Unit, Radboud University Medical Center, Nijmegen, the Netherlands) for their assistance during the adrenaline administration, and F. Vrieling (Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands, and Division of Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands), J. van Heck, M. Dumont and L. van Emst (all Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands) for their assistance in the lab. In addition, we would like to thank S. Teerenstra (Department of Statistics, Radboud University Medical Center, Nijmegen, the Netherlands) for his statistical assistance.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"Data supporting the findings of this study are available from the corresponding author upon reasonable request.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"This study has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement no. 777460. RIM is supported by a Dutch Diabetes Research Foundation Senior Fellowship, grant no. 2023.82.011. The study sponsor\/funder was not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"BEdG is a member of the Editorial Board of\n                      Diabetologia\n                      . The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"IFM, MSH, RS, CJT, BEdG and RIM designed the study, with the clinical and laboratory protocols designed by IFM and MSH, respectively. IFM and MSH performed the experiments and collected the data. IFM and MSH analysed and interpreted the data and drafted the manuscript. RS, CJT, BEdG and RIM critically reviewed the manuscript and provided substantial supervision. All authors discussed the results and implications and provided feedback on the manuscript at all stages. All the authors have approved the final version of the manuscript for publication. IFM, MSH and RIM are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}