{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T12:19:54Z","timestamp":1778069994726,"version":"3.51.4"},"reference-count":58,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      An exaggerated exercise pressor reflex and peripheral neuropathy are both evoked by the same type of thinly myelinated afferents and are present in patients with type 2 diabetes mellitus (T2DM). Although it is known that the pro\u2010inflammatory cytokine interleukin\u20101\u03b2 (IL\u20101\u03b2) contributes to peripheral neuropathy, the effects of IL\u20101\u03b2 on the exercise pressor reflex in T2DM are not known. Therefore, we aimed to determine the effect of IL\u20101 receptors on the exercise pressor reflex in T2DM. We compared changes in peak pressor (mean arterial pressure; \u0394MAP), blood pressure index (\u0394BPi), heart rate (\u0394HR) and heart rate index (\u0394HRi) responses to static and intermittent contractions and tendon stretch before and after peripheral IL\u20101 type 1 receptor blockade (anakinra, Kineret\n                      <jats:sup>\u00ae<\/jats:sup>\n                      ) in T2DM and healthy male rats and IL\u20101 receptor activation (IL\u20101\u03b2) in healthy rats. Blocking IL\u20101 receptors significantly attenuated the \u0394MAP and \u0394BPi to static contraction in T2DM rats. Furthermore, blocking IL\u20101 receptors significantly attenuated the \u0394MAP, \u0394BPi and \u0394HRi to intermittent contraction, and \u0394MAP to tendon stretch in T2DM rats (all\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). In addition, IL\u20101 receptor activation significantly exaggerated the \u0394MAP and \u0394BPi to static contraction and \u0394MAP, \u0394BPi and \u0394HR to intermittent contraction in healthy rats, all\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05. Furthermore, circulating IL\u20101\u03b2 serum concentrations were significantly greater in T2DM rats than in healthy rats (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). We conclude that IL\u20101 signalling contributes to the exaggerated exercise pressor reflex in T2DM, suggesting for the first time that inflammatory cytokines play a critical role in exaggerated blood pressure responses to exercise in those with T2DM.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16421-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Chronic inflammation, a complication of type 2 diabetes mellitus (T2DM), causes increased production of pro\u2010inflammatory cytokines, such as interleukin (IL)\u20101\u03b2, IL\u20106, and tumour necrosis factor\u2010\u03b1.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>IL\u20101\u03b2 has been shown to sensitize muscle afferents that conduct the exercise pressor reflex.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            We found blocking of IL\u20101 receptors by anakinra (Kineret\n                            <jats:sup>\u00ae<\/jats:sup>\n                            ), an IL\u20101 type 1 receptor antagonist, significantly attenuated the exaggerated exercise pressor reflex in T2DM rats, but not in healthy rats. In addition, activating IL\u20101 receptors with IL\u20101\u03b2 significantly augmented the exercise pressor reflex in healthy rats.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our findings suggest that IL\u20101 receptors, by mediating IL\u20101\u03b2 signalling, play a role in exaggerating the exercise pressor reflex in T2DM.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            These results highlight the complex interplay between inflammation and the autonomic nervous system in regulating cardiovascular function, and the potential for using an FDA\u2010approved IL\u20101 receptor antagonist, Kineret\n                            <jats:sup>\u00ae<\/jats:sup>\n                            , as a therapeutic approach to reduce adverse cardiovascular events during physical activity in those with T2DM.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp287120","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T21:53:37Z","timestamp":1731966817000},"page":"5009-5025","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Interleukin\u20101 type 1 receptor blockade attenuates the exaggerated exercise pressor reflex in male UC Davis type 2 diabetic mellitus rats"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9504-0018","authenticated-orcid":false,"given":"Yu","family":"Huo","sequence":"first","affiliation":[{"name":"Department of Kinesiology and Health Education The University of Texas at Austin  Austin TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6348-1786","authenticated-orcid":false,"given":"Milena","family":"Samora","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Health Education The University of Texas at Austin  Austin TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard K.","family":"McCuller","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Health Education The University of Texas at Austin  Austin TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimber L.","family":"Stanhope","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine and Department of Nutrition University of California Davis  Davis CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3652-8301","authenticated-orcid":false,"given":"Peter J.","family":"Havel","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine and Department of Nutrition University of California Davis  Davis CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9205-1961","authenticated-orcid":false,"given":"Michelle L.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Health Education The University of Texas at Austin  Austin TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0081-0244","authenticated-orcid":false,"given":"Audrey J.","family":"Stone","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Health Education The University of Texas at Austin  Austin TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1937.sp003485"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2013.04.036"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7840724"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.15826"},{"issue":"2","key":"e_1_2_5_6_1","first-page":"R451","article-title":"Increased interleukin 1 beta in human skeletal muscle after exercise","volume":"257","author":"Cannon J. G.","year":"1989","journal-title":"American Journal of Physiology"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1199"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2014.10.018"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1971.sp009498"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP271714"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00195.2015"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.90635.2008"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12621"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP284517"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/334698a0"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00229.2019"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1287392"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1744806916646784"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871530319666191022114139"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-1161"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00636.2015"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2020.104686"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.1063326"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.731877"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.15672"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01067.2012"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1983.55.1.105"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109075"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00061.2019"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.5152\/TJAR.2016.02212"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1972.sp009887"},{"issue":"1","key":"e_1_2_5_32_1","first-page":"6","article-title":"A synergistic relationship between TNF\u2010alpha, IL\u20101 beta, and TGF\u2010beta 1 on IL\u20106 secretion by the IEC\u20106 intestinal epithelial cell line","volume":"86","author":"McGee D. W.","year":"1995","journal-title":"Immunology"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.090074"},{"key":"e_1_2_5_34_1","doi-asserted-by":"crossref","DOI":"10.17226\/25801","volume-title":"Guide for the Care and Use of Laboratory Animals","author":"National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals","year":"2011"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2019.05.002"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0101com"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1993.tb08203.x"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP280892"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1900\/RDS.2007.4.98"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.3.327"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.12.3248.3248"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevEukaryotGeneExpr.2017019712"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4582-15.2016"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.01.021"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2023.103117"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00879.2023"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00368.2003"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajh.2008.166"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-021-01409-0"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2021.100307"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.00961.x"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-1317"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00587.2011"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.4103\/0971-5916.93435"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2007.06.003"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2012.01.001"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01461"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2005.04.018"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2007.05.023"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP287120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T16:12:11Z","timestamp":1762531931000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP287120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,18]]},"references-count":58,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1113\/JP287120"],"URL":"https:\/\/doi.org\/10.1113\/jp287120","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,18]]},"assertion":[{"value":"2024-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}