TY - JOUR
T1 - Ethanol feeding induces insulin resistance with enhanced PI 3-kinase activation
AU - Onishi, Yukiko
AU - Honda, Miho
AU - Ogihara, Takehide
AU - Sakoda, Hideyuki
AU - Anai, Motonobu
AU - Fujishiro, Midori
AU - Ono, Hiraku
AU - Shojima, Nobuhiro
AU - Fukushima, Yasushi
AU - Inukai, Kouichi
AU - Katagiri, Hideki
AU - Kikuchi, Masatoshi
AU - Oka, Yoshitomo
AU - Asano, Tomoichiro
PY - 2003/4/11
Y1 - 2003/4/11
N2 - 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.
AB - 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.
KW - Ethanol
KW - Euglycemic-hyperinsulinemic clamp study
KW - Insulin resistance
KW - Insulin signaling
KW - Phosphatidylinositol 3-kinase
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U2 - 10.1016/S0006-291X(03)00407-8
DO - 10.1016/S0006-291X(03)00407-8
M3 - Article
C2 - 12670480
AN - SCOPUS:0344211825
SN - 0006-291X
VL - 303
SP - 788
EP - 794
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -