{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:08:20Z","timestamp":1792271300610,"version":"4.4.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,4,7]]},"abstract":"<jats:p>\n                    Thyrotoxicosis increases endogenous glucose production (EGP) and induces hepatic insulin resistance. We have recently shown that these alterations can be modulated by selective hepatic sympathetic and parasympathetic denervation, pointing to neurally mediated effects of thyroid hormone on glucose metabolism. Here, we investigated the effects of central triiodothyronine (T\n                    <jats:sub>3<\/jats:sub>\n                    ) administration on EGP. We used stable isotope dilution to measure EGP before and after i.c.v. bolus infusion of T\n                    <jats:sub>3<\/jats:sub>\n                    or vehicle in euthyroid rats. To study the role of hypothalamic preautonomic neurons, bilateral T\n                    <jats:sub>3<\/jats:sub>\n                    microdialysis in the paraventricular nucleus (PVN) was performed for 2 h. Finally, we combined T\n                    <jats:sub>3<\/jats:sub>\n                    microdialysis in the PVN with selective hepatic sympathetic denervation to delineate the involvement of the sympathetic nervous system in the observed metabolic alterations. T\n                    <jats:sub>3<\/jats:sub>\n                    microdialysis in the PVN increased EGP by 11 \u00b1 4% (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.020), while EGP decreased by 5 \u00b1 8% (ns) in vehicle-treated rats (T\n                    <jats:sub>3<\/jats:sub>\n                    vs. Veh,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.030). Plasma glucose increased by 29 \u00b1 5% (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.0001) after T\n                    <jats:sub>3<\/jats:sub>\n                    microdialysis versus 8 \u00b1 3% in vehicle-treated rats (T\n                    <jats:sub>3<\/jats:sub>\n                    vs. Veh,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.003). Similar effects were observed after i.c.v. T\n                    <jats:sub>3<\/jats:sub>\n                    administration. Effects of PVN T\n                    <jats:sub>3<\/jats:sub>\n                    microdialysis were independent of plasma T\n                    <jats:sub>3<\/jats:sub>\n                    , insulin, glucagon, and corticosterone. However, selective hepatic sympathectomy completely prevented the effect of T\n                    <jats:sub>3<\/jats:sub>\n                    microdialysis on EGP. We conclude that stimulation of T\n                    <jats:sub>3<\/jats:sub>\n                    -sensitive neurons in the PVN of euthyroid rats increases EGP via sympathetic projections to the liver, independently of circulating glucoregulatory hormones. This represents a unique central pathway for modulation of hepatic glucose metabolism by thyroid hormone.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0805355106","type":"journal-article","created":{"date-parts":[[2009,3,24]],"date-time":"2009-03-24T22:29:06Z","timestamp":1237933746000},"page":"5966-5971","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":140,"title":["Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver"],"prefix":"10.1073","volume":"106","author":[{"given":"Lars P.","family":"Klieverik","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism,"},{"name":"Netherlands Institute for Neuroscience, 1105 BA, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah F.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism,"},{"name":"Netherlands Institute for Neuroscience, 1105 BA, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelieke van","family":"Riel","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism,"},{"name":"Netherlands Institute for Neuroscience, 1105 BA, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewout","family":"Foppen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism,"},{"name":"Netherlands Institute for Neuroscience, 1105 BA, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Bisschop","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille J.","family":"Serlie","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Boelen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u00ebtte T.","family":"Ackermans","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam,The Netherlands; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans P.","family":"Sauerwein","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Fliers","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andries","family":"Kalsbeek","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism,"},{"name":"Netherlands Institute for Neuroscience, 1105 BA, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,4,7]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"667","volume-title":"The Thyroid: A Fundamental and Clinical Text","author":"Franklyn JA","year":"2000","unstructured":"JA Franklyn, Metabolic changes in thyrotoxicosis. The Thyroid: A Fundamental and Clinical Text, eds LE Braverman, RD Utiger (Lippincott Williams & Wilkins, 8th Ed, Philadelphia), pp. 667\u2013672 (2000).","edition":"8"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-18584"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00659.2007"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0143"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.04.06.db05-1339"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2001.52"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1202-798"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn0602-861"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5328-03.2004"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0474"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.135.1.7516871"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02423-9"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3116669"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj1820565"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00009.2005"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.11.6323"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.1991.1.273"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0545"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03344003"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-2567"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.3.1097"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601600103"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.2.227"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2007.09.003"},{"key":"e_1_3_3_25_2","first-page":"2767","article-title":"Hypermetabolism in mice caused by the central action of an unliganded thyroid hormone receptor alpha1","volume":"145","author":"Sjogren M","year":"2007","unstructured":"M Sjogren, et al., Hypermetabolism in mice caused by the central action of an unliganded thyroid hormone receptor alpha1. 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J Clin Endocrinol Metab 81, 2828\u20132835 (1996).","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0080"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0667"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112146"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1959.tb44923.x"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.10.7709"},{"key":"e_1_3_3_35_2","first-page":"2220","article-title":"The quantification of gluconeogenesis in healthy men by (2)H2O and [2-(13)C]glycerol yields different results","volume":"86","author":"Ackermans MT","year":"2001","unstructured":"MT Ackermans, et al., The quantification of gluconeogenesis in healthy men by (2)H2O and [2-(13)C]glycerol yields different results. 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