M. Laine et al., INSULIN-RESISTANCE OF GLUCOSE-UPTAKE IN SKELETAL-MUSCLE CANNOT BE AMELIORATED BY ENHANCING ENDOTHELIUM-DEPENDENT BLOOD-FLOW IN OBESITY, The Journal of clinical investigation, 101(5), 1998, pp. 1156-1162
We tested the hypothesis that endothelium-dependent vasodilatation is
a determinant of insulin resistance of skeletal muscle glucose uptake
in human obesity, Eight obese (age 26+/-1 yr, body mass index 37 +/- 1
kg/m(2)) and seven nonobese males (25 +/- yr, 23 +/- 1 kg/m(2)) recei
ved an infusion of bradykinin into the femoral artery of one leg hinde
r intravenously maintained normoglycemic hyperinsulinemic conditions,
Blood flow was measured simultaneously in he bradykinin and insulin-an
d the insulin-infused leg before and during hyperinsulinemia using [O-
15]-labeled water ([O-15]H2O) and positron emission tomography (PET),
Glucose uptake was quantitated immediately thereafter in both legs usi
ng [F-18]-fluoro-deoxy-glucose ([F-18]PDG) and PET. Whole body insulin
-stimulated glucose uptake was lower Ire the obese (507+/-47 mu mol/m(
2).min) than the nonobese (1205+/-97 mu mol/m(2).min, P < 0.001) subje
cts. Muscle glucose uptake in the insulin-infused leg was 66% lower in
the obese (19+/-4 mu mol/kg muscle.min) than in the nonobese (56+/-9
mu mol/kg muscle.min, P < 0.005) subjects, Bradykinin increased blood
flow during hyperinsulinemia in the obese subjects (19+/-4 from 16 +/-
1 to 28+/-4 ml/kg muscle.min (P < 0.05), and in the normal subjects b
y 65% from 23+/-3 to 38+/-9 ml/kg muscle.min (P < 0.05), However, this
flow increase required twice as much bradykinin in the obese (51+/-3
mu g over 100 min) than in the normal(25+/-1 mu g, P < 0.001) subjects
, In the obese subjects, blood flow in the bradykinin and insulin-infu
sed leg (28 +/- 4 ml/kg muscle min) was comparable to that ire the ins
ulin-infused leg in the normal subjects during hyperinsulinemia (24+/-
5 ml/kg muscle min), Despite this, insulin-stimulated glucose uptake r
emained unchanged in the bradykinin and insulin-infused leg (18+/-4 mu
mol/kg.min) compared with the insulin-infused leg (19+/-4 mu mol/kg m
uscle min) in the obese subjects, Insulin-stimulated glucose uptake al
so was unaffected by bradykinin in the normal subjects (58+/-10 vs, 56
+/-9 mu mol/kg.min, bradykinin and insulin versus insulin leg), These
data demonstrate that obesity is characterized by two distinct defects
ire skeletal muscle: insulin resistance of cellular glucose extractio
n and impaired endothelium-dependent vasodilatation, Since a 75% incre
ase in blood flow does not alter glucose uptake, insulin resistance in
obesity cannot be overcome by normalizing muscle blood flow.