|Titolo:||Human delta opioid receptors stimulate glucose uptake through activation of the PI3K/Akt pathway|
|Data di pubblicazione:||2009|
|Abstract:||Glucose transport across plasma membrane is a key process for the cellular regulation of energy metabolism. In the present study we have examined the role of delta opioid receptors in the regulation of glucose uptake. The human delta opioid receptor was stably expressed in Chinese hamster ovary cells. We found that short-term exposure of cells to the delta opioid receptor agonists [D-Pen2,5]enkephalin (DPDPE) and SNC 80 caused a marked increase of the uptake of the nonmetabolizable glucose analog [3H]2-deoxy-D-glucose ([3H]-DG). The stimulatory effects of DPDPE and SNC 80 were concentration-dependent with EC50 values of 0.2 and 0.6 nM, respectively, and potently antagonized by the selective delta opioid receptor antagonist naltrindole. Pre-treatment of cells with pertussis toxin completely prevented the delta opioid receptor-induced stimulation of [3H]-DG uptake. Moreover, addition of wortmannin and LY 294002, which inhibit phosphatidylinositol-3 kinase (PI3K), or Akt inhibitor VIII, a preferential inhibitor of Akt-1/2, markedly reduced the stimulation of [3H]-DG uptake elicited by SNC 80. Under similar experimental conditions, cell treatment with either DPDPE or SNC 80 stimulated PI3K activity, as documented by the enhanced phosphorylation of Akt. These data indicate that activation of human delta opioid receptors can promote glucose uptake through a mechanism involving Gi/Go-dependent activation of PI3K/Akt signaling pathway. The stimulation of glucose uptake may participate in the protective effects of delta opioid agonists against cell damage induced by hypoxia or ischemia.|
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