The dietary flavonoids naringenin and quercetin acutely impair glucose metabolism in rodents possibly via inhibition of hypothalamic insulin signalling

Christiane E. Koch, Goutham K. Ganjam, Juliane Steger, Karen Legler, Sigrid Stoehr, Daniela Schumacher, Nigel Hoggard, Gerhard Heldmaier, Alexander Tups, Nigel Hoggard

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Secondary metabolites of herbs and spices are widely used as an alternative strategy in the therapy of various diseases. The polyphenols naringenin, quercetin and curcumin have been characterised as anti-diabetic agents. Conversely, in vitro, naringenin and quercetin are described to inhibit phosphoinositide-3-kinase (PI3K), an enzyme that is essential for the neuronal control of whole body glucose homoeostasis. Using both in vitro and in vivo experiments, we tested whether the inhibitory effect on PI3K occurs in neurons and if it might affect whole body glucose homoeostasis. Quercetin was found to inhibit basal and insulin-induced phosphorylation of Akt (Ser473), a downstream target of PI3K, in HT-22 cells, whereas naringenin and curcumin had no effect. In Djungarian hamsters (Phodopus sungorus) naringenin and quercetin (10 mg/kg administered orally) diminished insulin-induced phosphorylation of Akt (Ser473) in the arcuate nucleus, indicating a reduction in hypothalamic PI3K activity. In agreement with this finding, glucose tolerance in naringenin-treated hamsters (oral) and mice (oral and intracerebroventricular) was reduced compared with controls. Dietary quercetin also impaired glucose tolerance, whereas curcumin was ineffective. Circulating levels of insulin and insulin-like growth factor-binding protein were not affected by the polyphenols. Oral quercetin reduced the respiratory quotient, suggesting that glucose utilisation was impaired after treatment. These data demonstrate that low doses of naringenin and quercetin acutely and potently impair glucose homoeostasis. This effect may be mediated by inhibition of hypothalamic PI3K signalling. Whether chronic impairments in glucose homoeostasis occur after long-term application remains to be identified.

Original languageEnglish
Pages (from-to)1040-1051
Number of pages12
JournalBritish Journal of Nutrition
Volume109
Issue number6
Early online date1 Aug 2012
DOIs
Publication statusPublished - 28 Mar 2013

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Quercetin
Flavonoids
1-Phosphatidylinositol 4-Kinase
Rodentia
Insulin
Glucose
Curcumin
Homeostasis
Phodopus
Polyphenols
Phosphorylation
Insulin-Like Growth Factor Binding Proteins
Spices
Arcuate Nucleus of Hypothalamus
Glucose Intolerance
naringenin
Cricetinae
Neurons
Enzymes

Keywords

  • leptin
  • phosphoinositide-3-kinase/insulin receptor substrate signalling
  • arcuate nucleus
  • curcumin
  • glucose homoeostasis
  • cells
  • central-nervous-system
  • body-weight
  • performance liquid-chromatography
  • rat adipocytes
  • phosphatidylinositol 3-kinases
  • blood-brain-barrier

Cite this

The dietary flavonoids naringenin and quercetin acutely impair glucose metabolism in rodents possibly via inhibition of hypothalamic insulin signalling. / Koch, Christiane E.; Ganjam, Goutham K.; Steger, Juliane; Legler, Karen; Stoehr, Sigrid; Schumacher, Daniela; Hoggard, Nigel; Heldmaier, Gerhard; Tups, Alexander; Hoggard, Nigel.

In: British Journal of Nutrition, Vol. 109, No. 6, 28.03.2013, p. 1040-1051.

Research output: Contribution to journalArticle

Koch, Christiane E. ; Ganjam, Goutham K. ; Steger, Juliane ; Legler, Karen ; Stoehr, Sigrid ; Schumacher, Daniela ; Hoggard, Nigel ; Heldmaier, Gerhard ; Tups, Alexander ; Hoggard, Nigel. / The dietary flavonoids naringenin and quercetin acutely impair glucose metabolism in rodents possibly via inhibition of hypothalamic insulin signalling. In: British Journal of Nutrition. 2013 ; Vol. 109, No. 6. pp. 1040-1051.
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AU - Stoehr, Sigrid

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AB - Secondary metabolites of herbs and spices are widely used as an alternative strategy in the therapy of various diseases. The polyphenols naringenin, quercetin and curcumin have been characterised as anti-diabetic agents. Conversely, in vitro, naringenin and quercetin are described to inhibit phosphoinositide-3-kinase (PI3K), an enzyme that is essential for the neuronal control of whole body glucose homoeostasis. Using both in vitro and in vivo experiments, we tested whether the inhibitory effect on PI3K occurs in neurons and if it might affect whole body glucose homoeostasis. Quercetin was found to inhibit basal and insulin-induced phosphorylation of Akt (Ser473), a downstream target of PI3K, in HT-22 cells, whereas naringenin and curcumin had no effect. In Djungarian hamsters (Phodopus sungorus) naringenin and quercetin (10 mg/kg administered orally) diminished insulin-induced phosphorylation of Akt (Ser473) in the arcuate nucleus, indicating a reduction in hypothalamic PI3K activity. In agreement with this finding, glucose tolerance in naringenin-treated hamsters (oral) and mice (oral and intracerebroventricular) was reduced compared with controls. Dietary quercetin also impaired glucose tolerance, whereas curcumin was ineffective. Circulating levels of insulin and insulin-like growth factor-binding protein were not affected by the polyphenols. Oral quercetin reduced the respiratory quotient, suggesting that glucose utilisation was impaired after treatment. These data demonstrate that low doses of naringenin and quercetin acutely and potently impair glucose homoeostasis. This effect may be mediated by inhibition of hypothalamic PI3K signalling. Whether chronic impairments in glucose homoeostasis occur after long-term application remains to be identified.

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