Positron emission tomography permits noninvasive measurement of regional glucose uptake in vivo in humans. We employed this technique to determine the effect of FFA on glucose uptake in leg, arm, and heart muscles. Six normal men were studied twice under euglycemic hyperinsulinemic (serum insulin -500 pmol/liter) conditions, once during elevation of serum FFA by infusions of heparin and Intralipid (serum FFA 2.0±0.4 mmol/liter), and once during infusion of saline (serum FFA 0.1±0.01 mmol/liter). Regional glucose uptake rates were measured using positron emission tomography-derived 'Ffluoro-2-deoxy-D-glucose kinetics and the three Elevation of plasma FFA decreased whole body glucose uptake by 31±2% (1,960±130 vs. 2,860±250 Mmol/min, P < 0.01, FFA vs. saline study). This decrease was due to inhibition of glucose uptake in the heart by 30±8% (150±33 vs. 200±28 smol/min, P < 0.02), and in skeletal muscles; both when measured in femoral (1,594±261 vs. 2,272±328 Mmol/ min. 25+13%) and arm muscles (1,617±411 to 2,305±517Mmol/min, P < 0.02, 31±6%). Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.75, P < 0.005), and arm muscles (r = 0.69, P < 0.05) but not with glucose uptake in the heart (r = 0.04, NS). These data demonstrate that the glucose-FFA cycle operates in vivo in both heart and skeletal muscles in humans. (J.

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Defects in insulin stimulation of blood flow have been suggested to contribute to insulin resistance. To directly test whether glucose uptake can be altered by changing blood flow, we infused bradykinin (27 g over 100 min), an endothelium-dependent vasodilator, into the femoral artery of 12 normal subjects (age 25 Ϯ 1 yr, body mass index 22 Ϯ 1 kg ր m 2 ) after an overnight fast ( n ϭ 5) and during normoglycemic hyperinsulinemic ( n ϭ 7) conditions (serum insulin 465 Ϯ 11 pmol ր liter, 0-100 min). Blood flow was measured simultaneously in both femoral regions using and PET. During hyperinsulinemia, muscle blood flow was 58% higher in the bradykinin-infused (38 Ϯ 9 ml ր kg muscle и min) than in the control leg (24 Ϯ 5, P Ͻ 0.01). Femoral muscle glucose uptake was identical in both legs (60.6 Ϯ 9.5 vs. 58.7 Ϯ 9.0 mol ր kg и min, bradykinin-infused vs. control leg, NS). Glucose extraction by skeletal muscle was 44% higher in the control (2.6 Ϯ 0.2 mmol ր liter) than the bradykinin-infused leg (1.8 Ϯ 0.2 mmol ր liter, P Ͻ 0.01). When bradykinin was infused in the basal state, flow was 98% higher in the bradykinin-infused (58 Ϯ 12 ml ր kg muscle и min) than the control leg (28 Ϯ 6 ml ր kg muscle и min, P Ͻ 0.01) but rates of muscle glucose uptake were identical in both legs (10.1 Ϯ 0.9 vs. 10.6 Ϯ 0.8 mol ր kg и min). We conclude that bradykinin increases skeletal muscle blood flow but not muscle glucose uptake in vivo. These data provide direct evidence against the hypothesis that blood flow is an independent regulator of insulin-stimulated glucose uptake in humans. ( J. Clin. Invest . 1996. 97:1741-1747.)

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Striatal D2 dopamine receptor characteristics of nine male patients with alcohol dependence abstinent for 1-68 weeks and eight healthy male volunteers were studied in vivo with positron emission tomography. The selective D2 receptor ligand [11C]raclopride and equilibrium model was used for D2 receptor density (Bmax) and affinity (Kd) measurements. A trend for a decreased striatal D2 receptor density and for reduced D2 receptor affinity was observed in patients with alcohol dependence. These parameters were not statistically significantly different between alcoholics and controls, but the ratio between D2 receptor density and affinity (Bmax/Kd or the striatum/cerebellum ratio from the high specific activity scan) was highly significantly lower in alcoholics than that of controls. In conclusion, the low D2 dopamine receptor Bmax/Kd ratio (striatum/cerebellum ratio) indicates that specific aspects of striatal [11C]raclopride binding in vivo are deviant in alcoholics compared to controls. The result is compatible with a reduced avidity of striatal dopamine D2 receptors in alcoholics, which is in line with the idea that D2 dopaminergic mechanisms are involved in the biology of alcohol dependence in man.