Effects of Physiological Doses of Resveratrol and Quercetin on Glucose Metabolism in Primary Myotubes.

Effects of Physiological Doses of Resveratrol and Quercetin on Glucose Metabolism in Primary Myotubes.
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DOI:
10.3390/ijms22031384
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发表时间:
2021-01-30
影响因子:
5.6
通讯作者:
Portillo MP
Portillo MP
中科院分区:
生物学2区
文献类型:
--
作者:
Eseberri I;Laurens C;Miranda J;Louche K;Lasa A;Moro C;Portillo MP

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近年来,酚类化合物已成为应对胰岛素抵抗和糖尿病的一种选择。本研究的主要目的是:(1)证明生理剂量的白藜芦醇(RSV)或槲皮素(Q)可以影响人肌管的葡萄糖代谢;(2)确定AMP激活的蛋白激酶(AMPK)和蛋白激酶B -PKB-(Akt)通路是否参与了这种作用。此外,这些多酚对线粒体生物合成和脂肪酸氧化的影响进行了分析。将来自健康供体的肌管与0.1 μM RSV或10 μM Q培养24 h。用D[U-14 C]葡萄糖测定葡萄糖代谢,如糖原合成、葡萄糖氧化和乳酸产生。还评估了使用[1- 14 C]棕榈酸酯的β-氧化以及通过真实的时间PCR和蛋白质印迹的关键代谢基因和蛋白质的表达。尽管RSV和Q增加了pgc 1 α的表达,但它们没有显著改变葡萄糖氧化或β-氧化。在基础条件下,Q增加AMPK、胰岛素受体底物1(IRS-1)和AS 160磷酸化,在胰岛素刺激条件下增加糖原合成酶激酶3(GSK 3 β)。RSV使AMPK和GSK 3 β的磷酸化速率增加。这两种多酚都增加了胰岛素刺激的糖原合成,并减少了人体肌管中乳酸的产生。因此,生理剂量的RSV或Q可在人肌管中表现出抗糖尿病作用。
Phenolic compounds have emerged in recent years as an option to face insulin resistance and diabetes. The central aim of this study was: (1) to demonstrate that physiological doses of resveratrol (RSV) or quercetin (Q) can influence glucose metabolism in human myotubes, (2) to establish whether AMP-activated protein kinase (AMPK) and protein kinase B –PKB- (Akt) pathways are involved in this effect. In addition, the effects of these polyphenols on mitochondrial biogenesis and fatty acid oxidation were analysed. Myotubes from healthy donors were cultured for 24 h with either 0.1 μM of RSV or with 10 μM of Q. Glucose metabolism, such as glycogen synthesis, glucose oxidation, and lactate production, were measured with D[U-14C]glucose. β-oxidation using [1–14C]palmitate as well as the expression of key metabolic genes and proteins by Real Time PCR and Western blot were also assessed. Although RSV and Q increased pgc1α expression, they did not significantly change either glucose oxidation or β-oxidation. Q increased AMPK, insulin receptor substrate 1 (IRS-1), and AS160 phosphorylation in basal conditions and glycogen synthase kinase 3 (GSK3β) in insulin-stimulated conditions. RSV tended to increase the phosphorylation rates of AMPK and GSK3β. Both of the polyphenols increased insulin-stimulated glycogen synthesis and reduced lactate production in human myotubes. Thus, physiological doses of RSV or Q may exhibit anti-diabetic actions in human myotubes.
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