Hepatic insulin resistance induced by chronic hindlimb ischemia.
Peripheral vascular disease (PVD) has been reported to cause deterioration in insulin sensitivity. The precise mechanism of insulin resistance induced by PVD has not been clarified. To elucidate the mechanism causing impaired insulin action and glucose metabolism under peripheral ischemic conditions, we determined glucose turnover and glucose tolerance in hindlimb-ischemic (FAL) rats. The right femoral artery was ligated in hindlimb-ischemic (FAL) rats, while the artery was only exposed in the Sham operated (Sham) rats used as a control. Two weeks after the ligation, glucose tolerance was impaired and plasma insulin levels were significantly increased in FAL rats compared with Sham rats after intraperitoneal glucose loading (2 g kg(-1)). Under euglycemic hyperinsulinemic clamp conditions, the glucose infusion rate was significantly lower in FAL rats compared with Sham rats, but there was no significant difference in the glucose disappearance rate between the two groups. Hyperinsulinemia suppressed endogenous glucose production by 50% in Sham rats, while the suppression was 20% in FAL rats, indicating hepatic insulin resistance in FAL rats. mRNA analysis of isolated liver after the clamp experiment revealed that glucokinase mRNA, but not PEPCK and glucose-6-phosphatase mRNA, was significantly lower in FAL rats compared with Sham rats. In conclusion, chronic hindlimb ischemia impaired glucose tolerance associated with insulin resistance in the liver rather than the peripheral tissues.
Hatazaki
Masahiro
M
Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Matsuhisa
Munehide
M
Nakatani
Yoshihisa
Y
Yoshiuchi
Kazutomi
K
Kuroda
Akio
A
Hazama
Yoji
Y
Kaneto
Hideaki
H
Yamasaki
Yoshimitsu
Y
Hori
Masatsugu
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D017931:DNA Primers; D004195:Disease Models, Animal; D005263:Femoral Artery; D005941:Glucokinase / Q000235:genetics; D006614:Hindlimb / Q000098:blood supply*; D007333:Insulin Resistance; D007511:Ischemia / Q000503:physiopathology*; D008099:Liver / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001786:Blood Glucose; D017931:DNA Primers; D005941:Glucokinase