title: Ethanol feeding induces insulin resistance with enhanced PI 3-kinase activation.
abstract: High ethanol intake is considered to impair insulin sensitivity. In the present study, we investigated the acute and chronic effects of ethanol intake on glucose metabolism and insulin signal transduction. Hyperinsulinemic-euglycemic clamp studies revealed 70% and 51% decreases in the glucose infusion rate, 52% and 31% decreases in the glucose utilization rate, and 6.6- and 8.0-fold increases in hepatic glucose in continuous- and acute-ethanol-loaded rats, respectively. Despite the presence of insulin resistance, alcohol-fed rats showed enhanced tyrosine phosphorylation of insulin receptors, IRS-1 and IRS-2, induced by insulin injection via the portal vein. PI 3-kinase activities associated with IRSs and phosphotyrosine also increased significantly as compared with those of controls. These data suggest ethanol intake to be a factor leading to insulin resistance, regardless of whether it is a single or continuous intake. In addition, the insulin signaling step impaired by ethanol feeding is likely to be downstream from PI 3-kinase.
authors.affiliation: The Institute for Adult Diseases, Asahi Life Foundation, 1-9-14, Nishishinjuku, Shinjuku-ku, Tokyo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Onishi
authors.forename: Miho
authors.initials: M
authors.lastname: Honda
authors.forename: Takehide
authors.initials: T
authors.lastname: Ogihara
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakoda
authors.forename: Motonobu
authors.initials: M
authors.lastname: Anai
authors.forename: Midori
authors.initials: M
authors.lastname: Fujishiro
authors.forename: Hiraku
authors.initials: H
authors.lastname: Ono
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Shojima
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Fukushima
authors.forename: Kouichi
authors.initials: K
authors.lastname: Inukai
authors.forename: Hideki
authors.initials: H
authors.lastname: Katagiri
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Oka
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000378:metabolism; D000818:Animals; D003847:Deoxyglucose / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D015309:Glucose Clamp Technique; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014443:Tyrosine / Q000737:chemistry
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D010750:Phosphoproteins; D000431:Ethanol; D014443:Tyrosine; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin