title: Opposite effects of quercetin, luteolin, and epigallocatechin gallate on insulin sensitivity under normal and inflammatory conditions in mice.
abstract: Flavonoids are polyphenolic compounds ubiquitous in plants. Quercetin, luteolin, and epigallocatechin gallate (EGCG) are flavonoids with a number of biochemical and cellular actions relevant to glucose homeostasis, but their regulation of insulin action is still uncertain. This study aims to evaluate the regulation of insulin action by quercetin, luteolin, and EGCG under normal and inflammatory conditions in mice. Oral administration of quercetin, luteolin, and EGCG impaired glucose tolerance and blunted the effect of insulin to low blood glucose. Luteolin and EGCG, but not quercetin, inhibited glucose load-induced insulin receptor substrate-1(IRS-1) tyrosine and Akt phosphorylation in adipose tissue. Meanwhile, insulin-stimulated glucose uptake was also inhibited by these flavonoids. We induced insulin resistance in mice by treatment with activated macrophages-derived conditioned medium (Mac-CM) and observed that quercetin, luteolin, and EGCG reversed glucose intolerance with improving insulin sensitivity. Quercetin, luteolin, and EGCG inhibited inflammation-evoked IKKβ activation and IRS-1 serine phosphorylation in adipose tissue, and thereby effectively restored glucose load-stimulated IRS-1 tyrosine and Akt phosphorylation, leading to an increase in insulin-mediated glucose uptake in adipocytes. The aforementioned results showed opposite effects of quercetin, luteolin, and EGCG on insulin sensitivity in mice. The different modulation of IRS-1 function by phosphorylating modification under normal and inflammatory conditions should be a key controlling for their action in regulation of insulin sensitivity.
authors: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China.
authors: Lu
authors: L
authors: Shao
authors: Kang
authors: K
authors: Liu
authors: Fang
authors: F
authors: Huang
authors: Xudan
authors: X
authors: Guo
authors: Min
authors: M
authors: Wang
authors: Baolin
authors: B
authors: Liu
mesh_terms: D016475:3T3 Cells; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D017077:Culture Media, Conditioned; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation; D055504:Insulin Receptor Substrate Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007333:Insulin Resistance; D047311:Luteolin / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D017077:Culture Media, Conditioned; D055504:Insulin Receptor Substrate Proteins; D002392:Catechin; D011794:Quercetin; C045651:epigallocatechin gallate; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; D005947:Glucose; D047311:Luteolin