Standard

Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver. / Klieverik, Lars P.; Janssen, Sarah F.; van Riel, Annelieke et al.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 14, 2009, p. 5966-5971.

Research output: Contribution to journalArticleAcademicpeer-review

Harvard

APA

Vancouver

Author

Klieverik, Lars P. ; Janssen, Sarah F. ; van Riel, Annelieke et al. / Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 14. pp. 5966-5971.

BibTeX

@article{18054d812b6f46879b1feebeef419286,
title = "Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver",
abstract = "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-3) administration on EGP. We used stable isotope dilution to measure EGP before and after i.c.v. bolus infusion of T-3 or vehicle in euthyroid rats. To study the role of hypothalamic preautonomic neurons, bilateral T-3 microdialysis in the paraventricular nucleus (PVN) was performed for 2 h. Finally, we combined T-3 microdialysis in the PVN with selective hepatic sympathetic denervation to delineate the involvement of the sympathetic nervous system in the observed metabolic alterations. T-3 microdialysis in the PVN increased EGP by 11 +/- 4% (P = 0.020), while EGP decreased by 5 +/- 8%(ns) in vehicle-treated rats (T-3 vs. Veh, P = 0.030). Plasma glucose increased by 29 +/- 5% (P = 0.0001) after T-3 microdialysis versus 8 +/- 3% in vehicle-treated rats (T-3 vs. Veh, P = 0.003). Similar effects were observed after i.c.v. T-3 administration. Effects of PVN T-3 microdialysis were independent of plasma T-3, insulin, glucagon, and corticosterone. However, selective hepatic sympathectomy completely prevented the effect of T-3 microdialysis on EGP. We conclude that stimulation of T-3-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",
author = "Klieverik, {Lars P.} and Janssen, {Sarah F.} and {van Riel}, Annelieke and Ewout Foppen and Bisschop, {Peter H.} and Serlie, {Mireille J.} and Anita Boelen and Ackermans, {Mari{\"e}tte T.} and Sauerwein, {Hans P.} and Eric Fliers and Andries Kalsbeek",
year = "2009",
doi = "10.1073/pnas.0805355106",
language = "English",
volume = "106",
pages = "5966--5971",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "14",

}

RIS

TY - JOUR

T1 - Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver

AU - Klieverik, Lars P.

AU - Janssen, Sarah F.

AU - van Riel, Annelieke

AU - Foppen, Ewout

AU - Bisschop, Peter H.

AU - Serlie, Mireille J.

AU - Boelen, Anita

AU - Ackermans, Mariëtte T.

AU - Sauerwein, Hans P.

AU - Fliers, Eric

AU - Kalsbeek, Andries

PY - 2009

Y1 - 2009

N2 - 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-3) administration on EGP. We used stable isotope dilution to measure EGP before and after i.c.v. bolus infusion of T-3 or vehicle in euthyroid rats. To study the role of hypothalamic preautonomic neurons, bilateral T-3 microdialysis in the paraventricular nucleus (PVN) was performed for 2 h. Finally, we combined T-3 microdialysis in the PVN with selective hepatic sympathetic denervation to delineate the involvement of the sympathetic nervous system in the observed metabolic alterations. T-3 microdialysis in the PVN increased EGP by 11 +/- 4% (P = 0.020), while EGP decreased by 5 +/- 8%(ns) in vehicle-treated rats (T-3 vs. Veh, P = 0.030). Plasma glucose increased by 29 +/- 5% (P = 0.0001) after T-3 microdialysis versus 8 +/- 3% in vehicle-treated rats (T-3 vs. Veh, P = 0.003). Similar effects were observed after i.c.v. T-3 administration. Effects of PVN T-3 microdialysis were independent of plasma T-3, insulin, glucagon, and corticosterone. However, selective hepatic sympathectomy completely prevented the effect of T-3 microdialysis on EGP. We conclude that stimulation of T-3-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

AB - 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-3) administration on EGP. We used stable isotope dilution to measure EGP before and after i.c.v. bolus infusion of T-3 or vehicle in euthyroid rats. To study the role of hypothalamic preautonomic neurons, bilateral T-3 microdialysis in the paraventricular nucleus (PVN) was performed for 2 h. Finally, we combined T-3 microdialysis in the PVN with selective hepatic sympathetic denervation to delineate the involvement of the sympathetic nervous system in the observed metabolic alterations. T-3 microdialysis in the PVN increased EGP by 11 +/- 4% (P = 0.020), while EGP decreased by 5 +/- 8%(ns) in vehicle-treated rats (T-3 vs. Veh, P = 0.030). Plasma glucose increased by 29 +/- 5% (P = 0.0001) after T-3 microdialysis versus 8 +/- 3% in vehicle-treated rats (T-3 vs. Veh, P = 0.003). Similar effects were observed after i.c.v. T-3 administration. Effects of PVN T-3 microdialysis were independent of plasma T-3, insulin, glucagon, and corticosterone. However, selective hepatic sympathectomy completely prevented the effect of T-3 microdialysis on EGP. We conclude that stimulation of T-3-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

U2 - 10.1073/pnas.0805355106

DO - 10.1073/pnas.0805355106

M3 - Article

C2 - 19321430

VL - 106

SP - 5966

EP - 5971

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 14

ER -

ID: 896376