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Glucocorticoid Signaling in the Arcuate Nucleus Modulates Hepatic Insulin Sensitivity. / Yi, Chun-Xia; Foppen, Ewout; Abplanalp, William et al.

In: Diabetes, Vol. 61, No. 2, 2012, p. 339-345.

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Yi, Chun-Xia ; Foppen, Ewout ; Abplanalp, William et al. / Glucocorticoid Signaling in the Arcuate Nucleus Modulates Hepatic Insulin Sensitivity. In: Diabetes. 2012 ; Vol. 61, No. 2. pp. 339-345.

BibTeX

@article{d5c26c5f20194d51892ebb271b48bb40,
title = "Glucocorticoid Signaling in the Arcuate Nucleus Modulates Hepatic Insulin Sensitivity",
abstract = "Glucocorticoid receptors are highly expressed in the hypothalamic paraventricular nucleus (PVN) and arcuate nucleus (ARC). As glucocorticoids have pronounced effects on neuropeptide Y (NPY) expression and as NPY neurons projecting from the ARC to the PVN are pivotal for balancing feeding behavior and glucose metabolism, we investigated the effect of glucocorticoid signaling in these areas on endogenous glucose production (EGP) and insulin sensitivity by local retrodialysis of the glucocorticoid receptor agonist dexamethasone into the ARC or the PVN, in combination with isotope dilution and hyperinsulinemic-euglycemic clamp techniques. Retrodialysis of dexamethasone for 90 min into the ARC or the PVN did not have significant effects on basal plasma glucose concentration. During the hyperinsulinemic-euglycemic clamp, retrodialysis of dexamethasone into the ARC largely prevented the suppressive effect of hyperinsulinemia on EGP. Antagonizing the NPY1 receptors by intracerebroventricular infusion of its antagonist largely blocked the hepatic insulin resistance induced by dexamethasone in the ARC. The dexamethasone-ARC-induced inhibition of hepatic insulin sensitivity was also prevented by hepatic sympathetic denervation. These data suggest that glucocorticoid signaling specifically in the ARC neurons modulates hepatic insulin responsiveness via NPY and the sympathetic system, which may add to our understanding of the metabolic impact of clinical conditions associated with hypercortisolism. Diabetes 61:339-345, 2012",
author = "Chun-Xia Yi and Ewout Foppen and William Abplanalp and Yuanqing Gao and Anneke Alkemade and {la Fleur}, {Susanne E.} and Serlie, {Mireille J.} and Eric Fliers and Buijs, {Ruud M.} and Tsch{\"o}p, {Matthias H.} and Andries Kalsbeek",
year = "2012",
doi = "10.2337/db11-1239",
language = "English",
volume = "61",
pages = "339--345",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "2",

}

RIS

TY - JOUR

T1 - Glucocorticoid Signaling in the Arcuate Nucleus Modulates Hepatic Insulin Sensitivity

AU - Yi, Chun-Xia

AU - Foppen, Ewout

AU - Abplanalp, William

AU - Gao, Yuanqing

AU - Alkemade, Anneke

AU - la Fleur, Susanne E.

AU - Serlie, Mireille J.

AU - Fliers, Eric

AU - Buijs, Ruud M.

AU - Tschöp, Matthias H.

AU - Kalsbeek, Andries

PY - 2012

Y1 - 2012

N2 - Glucocorticoid receptors are highly expressed in the hypothalamic paraventricular nucleus (PVN) and arcuate nucleus (ARC). As glucocorticoids have pronounced effects on neuropeptide Y (NPY) expression and as NPY neurons projecting from the ARC to the PVN are pivotal for balancing feeding behavior and glucose metabolism, we investigated the effect of glucocorticoid signaling in these areas on endogenous glucose production (EGP) and insulin sensitivity by local retrodialysis of the glucocorticoid receptor agonist dexamethasone into the ARC or the PVN, in combination with isotope dilution and hyperinsulinemic-euglycemic clamp techniques. Retrodialysis of dexamethasone for 90 min into the ARC or the PVN did not have significant effects on basal plasma glucose concentration. During the hyperinsulinemic-euglycemic clamp, retrodialysis of dexamethasone into the ARC largely prevented the suppressive effect of hyperinsulinemia on EGP. Antagonizing the NPY1 receptors by intracerebroventricular infusion of its antagonist largely blocked the hepatic insulin resistance induced by dexamethasone in the ARC. The dexamethasone-ARC-induced inhibition of hepatic insulin sensitivity was also prevented by hepatic sympathetic denervation. These data suggest that glucocorticoid signaling specifically in the ARC neurons modulates hepatic insulin responsiveness via NPY and the sympathetic system, which may add to our understanding of the metabolic impact of clinical conditions associated with hypercortisolism. Diabetes 61:339-345, 2012

AB - Glucocorticoid receptors are highly expressed in the hypothalamic paraventricular nucleus (PVN) and arcuate nucleus (ARC). As glucocorticoids have pronounced effects on neuropeptide Y (NPY) expression and as NPY neurons projecting from the ARC to the PVN are pivotal for balancing feeding behavior and glucose metabolism, we investigated the effect of glucocorticoid signaling in these areas on endogenous glucose production (EGP) and insulin sensitivity by local retrodialysis of the glucocorticoid receptor agonist dexamethasone into the ARC or the PVN, in combination with isotope dilution and hyperinsulinemic-euglycemic clamp techniques. Retrodialysis of dexamethasone for 90 min into the ARC or the PVN did not have significant effects on basal plasma glucose concentration. During the hyperinsulinemic-euglycemic clamp, retrodialysis of dexamethasone into the ARC largely prevented the suppressive effect of hyperinsulinemia on EGP. Antagonizing the NPY1 receptors by intracerebroventricular infusion of its antagonist largely blocked the hepatic insulin resistance induced by dexamethasone in the ARC. The dexamethasone-ARC-induced inhibition of hepatic insulin sensitivity was also prevented by hepatic sympathetic denervation. These data suggest that glucocorticoid signaling specifically in the ARC neurons modulates hepatic insulin responsiveness via NPY and the sympathetic system, which may add to our understanding of the metabolic impact of clinical conditions associated with hypercortisolism. Diabetes 61:339-345, 2012

U2 - 10.2337/db11-1239

DO - 10.2337/db11-1239

M3 - Article

C2 - 22210324

VL - 61

SP - 339

EP - 345

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 2

ER -

ID: 1560366