Ethanol feeding induces insulin resistance with enhanced PI 3-kinase activation.
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.
Onishi
Yukiko
Y
The Institute for Adult Diseases, Asahi Life Foundation, 1-9-14, Nishishinjuku, Shinjuku-ku, Tokyo, Japan.
Honda
Miho
M
Ogihara
Takehide
T
Sakoda
Hideyuki
H
Anai
Motonobu
M
Fujishiro
Midori
M
Ono
Hiraku
H
Shojima
Nobuhiro
N
Fukushima
Yasushi
Y
Inukai
Kouichi
K
Katagiri
Hideki
H
Kikuchi
Masatoshi
M
Oka
Yoshitomo
Y
Asano
Tomoichiro
T
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
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