Evidence for Dissociation of Insulin Stimulation of Blood Flow and Glucose Uptake in Human Skeletal Muscle: Studies Using [15O]H2O, [18F]fluoro-2-deoxy-D-glucose, and Positron Emission Tomography

Abstract

We determined the effect of insulin on muscle blood flow and glucose uptake in humans using [15O]H2O, [18F]fluoro-2-deoxy-D-glucose ([18F]FDG), and positron emission tomography (PET). Femoral muscle blood flow was measured in 14 healthy volunteers (age 34 +/- 8 years, BMI 24.6 +/- 3.4 kg/m2 [means +/- SD]) before and at 75 min during a 140-min high-dose insulin infusion (serum insulin 2,820 +/- 540 pmol/l) under normoglycemic conditions. A dynamic scan of the femoral region was performed using PET for 6 min after injection of [15O]H2O to determine the 15O concentration in tissue. Regional femoral muscle blood flow was calculated using an autoradiographic method from the dynamic data obtained with PET and [15O]H2O. Femoral muscle glucose uptake was measured during hyperinsulinemia immediately after the flow measurement using PET-derived [18F]FDG kinetics and a three-compartment model. Whole-body glucose uptake was quantitated using the euglycemic insulin clamp technique. In the basal state, 84 +/- 8% of blood flow was confined to skeletal muscle. Insulin increased leg blood flow from 29 +/- 14 to 54 +/- 29 ml x kg-1 leg x min-1 (P < 0.001) and muscle flow from 31 +/- 18 to 58 +/- 35 ml x kg-1 muscle x min-1 (P < 0.005). Under insulin-stimulated conditions, 81 +/- 8% of blood flow was in muscle tissue (NS versus basal). Skeletal muscle explained 70 +/- 25% of the increase in leg blood flow. No correlation was observed between blood flow and glucose uptake when analyzed individually in identical regions of interest within femoral muscles. These data demonstrate that skeletal muscle accounts for most of the insulin-induced increase in blood flow. Insulin-stimulated rates of blood flow and glucose uptake do not colocalize in the same regions of muscle tissue, suggesting that insulin's hemodynamic and metabolic effects are differentially regulated.

Interactions Among Glucose Delivery, Transport, and Phosphorylation That Underlie Skeletal Muscle Insulin Resistance in Obesity and Type 2 Diabetes: Studies With Dynamic PET Imaging

“…The time–tissue activity curves for 3-OMG reflect an integration of these two reversible processes (12,20,28), which the current study distinguished using sequential imaging with [ 15 O]H 2 O and [ 11 C]3-OMG. Insulin-stimulated rates of muscle tissue perfusion were similar across subject groups and are similar to those reported previously for normal weight subjects (34). These rates corresponded very well with kinetic values for tissue perfusion attributed to k 1 ascertained for [ 11 C]3-OMG and [ 18 F]FDG.…”

Heterogeneity in insulin-stimulated glucose uptake among different muscle groups in healthy lean people and people with obesity

“…However, we did not detect an association between muscle perfusion and glucose uptake rates in individual muscle groups or all muscles combined in either the lean or obese groups or all participants combined. These findings confirm and extend the results from previous studies that found there was no association between insulin-stimulated thigh muscle perfusion and thigh muscle glucose uptake rates [32][33][34]. These data suggest that insulin delivery and glucose delivery to muscles are not rate limiting for insulin-stimulated glucose uptake and that local factors likely determine insulin action and glucose transport into myocytes.…”

Glucocorticoids and insulin resistance: old hormones, new targets

“…Moreover, this model suggests that the impaired endothelium-dependent vasodilatation in subjects with features of the metabolic syndrome (hypercholesterolaemia [45], hypertension [46] or diabetes mellitus) could both result from, and contribute to, impaired insulin action in skeletal muscle. However, others have found that increased blood flow and glucose uptake during hyperinsulinaemia are dissociated in man [47].…”