title: Acute vascular and metabolic actions of the green tea polyphenol epigallocatechin 3-gallate in rat skeletal muscle.
abstract: Epidemiological studies show a dose-dependent relationship between green tea consumption and reduced risk for type 2 diabetes and cardiovascular disease. Bioactive compounds in green tea including the polyphenol epigallocatechin 3-gallate (EGCG) have insulin-mimetic actions on glucose metabolism and vascular function in isolated cell culture studies. The aim of this study is to explore acute vascular and metabolic actions of EGCG in skeletal muscle of Sprague-Dawley rats. Direct vascular and metabolic actions of EGCG were investigated using surgically isolated constant-flow perfused rat hindlimbs. EGCG infused at 0.1, 1, 10 and 100 μM in 15 min step-wise increments caused dose-dependent vasodilation in 5-hydroxytryptamine pre-constricted hindlimbs. This response was not impaired by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin or the AMP-kinase inhibitor Compound C. The nitric oxide synthase (NOS) inhibitor NG-Nitro-l-Arginine Methyl Ester (L-NAME) completely blocked EGCG-mediated vasodilation at 0.1-10 μM, but not at 100 μM. EGCG at 10 μM did not alter muscle glucose uptake nor did it augment insulin-stimulated muscle glucose uptake. The acute metabolic and vascular actions of 10 μM EGCG in vivo were investigated in anaesthetised rats during a hyperinsulinemic-euglycemic clamp (10 mU min-1kg-1insulin). EGCG and insulin both stimulated comparable increases in muscle microvascular blood flow without an additive effect. EGCG-mediated microvascular action occurred without altering whole body or muscle glucose uptake. We concluded that EGCG has direct NOS-dependent vasodilator actions in skeletal muscle that do not acutely alter muscle glucose uptake or enhance the vascular and metabolic actions of insulin in healthy rats.
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
authors.forename: Huei L H
authors.initials: HLH
authors.lastname: Ng
authors.affiliation: School of Medicine, University of Tasmania, Hobart, Australia.
authors.forename: Dino
authors.initials: D
authors.lastname: Premilovac
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rattigan
authors.affiliation: School of Medicine, University of Tasmania, Hobart, Australia.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Richards
authors.affiliation: Diabetes, Endocrinology, and Obesity Branch, NIDDK, National Institutes of Health, Bethesda, USA.
authors.forename: Ranganath
authors.initials: R
authors.lastname: Muniyappa
authors.affiliation: University of Maryland, Division of Endocrinology, Diabetes & Nutrition, Baltimore, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Quon
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia. Electronic address: Michelle.Keske@utas.edu.au.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Keske
mesh_terms: D000818:Animals; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009924:Organ Culture Techniques; D010477:Perfusion; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D007328:Insulin; D012701:Serotonin; D002392:Catechin; C045651:epigallocatechin gallate; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester
keywords: Endothelium; Epigallocatechin 3-gallate; Green tea; Metabolism; Microvascular; Skeletal muscle