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.