Central administration of resveratrol improves diet-induced diabetes

Giorgio Ramadori, Laurent Gautron, Teppei Fujikawa, Claudia R. Vianna, Joel K. Elmquist, Roberto Coppari

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Resveratrol is a natural polyphenolic compound that activates nicotinamide adenosine dinucleotide-dependent deacetylase SIRT1. Resveratrol has recently been shown to exert potent antidiabetic actions when orally delivered to animal models of type 2 diabetes. However, the tissue(s) mediating these beneficial effects is unknown. Because SIRT1 is expressed in central nervous system (CNS) neurons known to control glucose and insulin homeostasis, we hypothesized that resveratrol antidiabetic effects are mediated by the brain. Here, we report that long-term intracerebroventricular infusion of resveratrol normalizes hyperglycemia and greatly improves hyperinsulinemia in diet-induced obese and diabetic mice. It is noteworthy that these effects are independent of changes in body weight, food intake, and circulating leptin levels. In addition, CNS resveratrol delivery improves hypothalamic nuclear factor-κB inflammatory signaling by reducing acetylated-RelA/p65 and total RelA/p65 protein contents, and inhibitor of nuclear factor-κB α and IκB kinase β mRNA levels. Furthermore, this treatment leads to reduced hepatic phosphoenolpyruvate carboxykinase 1 mRNA and protein levels and ameliorates pyruvate-induced hyperglycemia in this mouse model of type 2 diabetes. Collectively, our results unveiled a previously unrecognized key role for the CNS in mediating the antidiabetic actions of resveratrol.

Original languageEnglish (US)
Pages (from-to)5326-5333
Number of pages8
JournalEndocrinology
Volume150
Issue number12
DOIs
StatePublished - Dec 2009

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Diet
Hypoglycemic Agents
Central Nervous System
Hyperglycemia
Type 2 Diabetes Mellitus
Intraventricular Infusions
Obese Mice
Messenger RNA
Phosphoenolpyruvate
Body Weight Changes
Niacinamide
Hyperinsulinism
Leptin
Pyruvic Acid
Adenosine
resveratrol
Proteins
Homeostasis
Phosphotransferases
Animal Models

ASJC Scopus subject areas

  • Endocrinology

Cite this

Central administration of resveratrol improves diet-induced diabetes. / Ramadori, Giorgio; Gautron, Laurent; Fujikawa, Teppei; Vianna, Claudia R.; Elmquist, Joel K.; Coppari, Roberto.

In: Endocrinology, Vol. 150, No. 12, 12.2009, p. 5326-5333.

Research output: Contribution to journalArticle

Ramadori, Giorgio ; Gautron, Laurent ; Fujikawa, Teppei ; Vianna, Claudia R. ; Elmquist, Joel K. ; Coppari, Roberto. / Central administration of resveratrol improves diet-induced diabetes. In: Endocrinology. 2009 ; Vol. 150, No. 12. pp. 5326-5333.
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