Central resistin induces hepatic insulin resistance via neuropeptide Y.

Central resistin induces hepatic insulin resistance via neuropeptide Y. Research Abstract Details 

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Central resistin induces hepatic insulin resistance via neuropeptide Y. Abstract Text:

Neel S Singhal,Mitchell A Lazar,Rexford S Ahima,Neel S Singhal,Mitchell A Lazar,Rexford S Ahima,

Sensing of peripheral hormones and nutrients by the hypothalamus plays an important role in maintaining peripheral glucose homeostasis. The hormone resistin impairs the response to insulin in liver and other peripheral tissues. Here we demonstrate that in normal mice resistin delivered in the lateral cerebral ventricle increased endogenous glucose production during hyperinsulinemic-euglycemic clamp, consistent with induction of hepatic insulin resistance. In agreement, central resistin inhibited Akt phosphorylation and increased the expression of glucose-6-phosphatase, the enzyme regulating glucose output in the liver. Central resistin induced expression of proinflammatory cytokines as well as suppressor of cytokine signaling-3, a negative regulator of insulin action in liver. Central infusion of resistin was associated with neuronal activation in the arcuate, paraventricular and dorsomedial nuclei, and increased neuropeptide Y (NPY) expression in the hypothalamus. The effects of central resistin on glucose production as well as hepatic expression of proinflammatory cytokines were abrogated in mice lacking NPY. Pretreatment of wild-type mice with antagonists of the NPY Y1 receptor, but not the Y5 receptor, also prevented the effects of central resistin. Together, these results suggest that resistin action on NPY neurons is an important regulator of hepatic insulin sensitivity.

Central resistin induces hepatic insulin resistance via neuropeptide Y. Publishing Authors By Initials

NS Singhal,MA Lazar,RS Ahima,NS Singhal,MA Lazar,RS Ahima,

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Central resistin induces hepatic insulin resistance via neuropeptide Y. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of neuroscience : the official journal

VOLUME: 27

Page Numbers: 12924-32

Journal Abbreviation: J. Neurosci.

ISSN: 1529-2401

DAY: 21

MONTH: Nov

YEAR: 2007

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LANGUAGE: eng

NlmUniqueID: 8102140

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Grant and Affiliation Information for Central resistin induces hepatic insulin resistance via neuropeptide Y.

AFFILIATION: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: P30 DK019525

ACRONYM: DK

MEDLINETA: J Neurosci

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