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J Clin Invest. 2007 Jun;117(6):1670-8. Epub 2007 May 24.

Hypothalamic resistin induces hepatic insulin resistance.

Author information

1
Department of Molecular Pharmacology, Albert Einstein College of Medicine of Yeshiva University, New York, NY 10461, USA.

Abstract

Circulating resistin stimulates endogenous glucose production (GP). Here, we report that bi-directional changes in hypothalamic resistin action have dramatic effects on GP and proinflammatory cytokine expression in the liver. The infusion of either resistin or an active cysteine mutant in the third cerebral ventricle (icv) or in the mediobasal hypothalamus stimulated GP independent of changes in circulating levels of glucoregulatory hormones. Conversely, central antagonism of resistin action markedly diminished the ability of circulating resistin to enhance GP. We also report that centrally mediated mechanisms partially control resistin-induced expression of TNF-alpha, IL-6, and SOCS-3 in the liver. These results unveil what we believe to be a novel site of action of resistin on GP and inflammation and suggest that hypothalamic resistin action can contribute to hyperglycemia in type 2 diabetes mellitus.

PMID:
17525801
PMCID:
PMC1868785
DOI:
10.1172/JCI30440
[Indexed for MEDLINE]
Free PMC Article

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