scholarly journals Quantitative Assessment of Glucose Transport in Human Skeletal Muscle: Dynamic Positron Emission Tomography Imaging of [O-Methyl-11C]3-O-Methyl-d-Glucose

2005 ◽  
Vol 90 (3) ◽  
pp. 1752-1759 ◽  
Author(s):  
Alessandra Bertoldo ◽  
Julie Price ◽  
Chet Mathis ◽  
Scott Mason ◽  
Daniel Holt ◽  
...  

Insulin-stimulated glucose transport in skeletal muscle is regarded as a key determinant of insulin sensitivity, yet isolation of this step for quantification in human studies is a methodological challenge. One notable approach is physiological modeling of dynamic positron emission tomography (PET) imaging using 2-[18-fluoro]2-deoxyglucose ([18F]FDG); however, this has a potential limitation in that deoxyglucose undergoes phosphorylation subsequent to transport, complicating separate estimations of these steps. In the current study we explored the use of dynamic PET imaging of [11C]3-O-methylglucose ([11C]3-OMG), a glucose analog that is limited to bidirectional glucose transport. Seventeen lean healthy volunteers with normal insulin sensitivity participated; eight had imaging during basal conditions, and nine had imaging during euglycemic insulin infusion at 30 mU/min·m2. Dynamic PET imaging of calf muscles was conducted for 90 min after the injection of [11C]3-OMG. Spectral analysis of tissue activity indicated that a model configuration of two reversible compartments gave the strongest statistical fit to the kinetic pattern. Accordingly, and consistent with the structure of a model previously used for [18F]FDG, a two-compartment model was applied. Consistent with prior [18F]FDG findings, insulin was found to have minimal effect on the rate constant for movement of [11C]3-OMG from plasma to tissue interstitium. However, during insulin infusion, a robust and highly significant increase was observed in the kinetics of inward glucose transport; this and the estimated tissue distribution volume for [11C]3-OMG increased 6-fold compared with basal conditions. We conclude that dynamic PET imaging of [11C]3-OMG offers a novel quantitative approach that is both chemically specific and tissue specific for in vivo assessment of glucose transport in human skeletal muscle.

2020 ◽  
Vol 21 (18) ◽  
pp. 6523
Author(s):  
Maria Vittoria Mattoli ◽  
Giorgio Treglia ◽  
Maria Lucia Calcagni ◽  
Annunziato Mangiola ◽  
Carmelo Anile ◽  
...  

Idiopathic normal pressure hydrocephalus (iNPH) is the only form of dementia that can be cured by surgery. Its diagnosis relies on clinical and radiological criteria. Identifying patients who can benefit from surgery is challenging, as other neurological diseases can be concomitant or mimic iNPH. We performed a systematic review on the role of positron emission tomography (PET) in iNPH. We retrieved 35 papers evaluating four main functional aspects with different PET radiotracers: (1) PET with amyloid tracers, revealing Alzheimer’s disease (AD) pathology in 20–57% of suspected iNPH patients, could be useful in predictions of surgical outcome. (2) PET with radiolabeled water as perfusion tracer showed a global decreased cerebral blood flow (CBF) and regional reduction of CBF in basal ganglia in iNPH; preoperative perfusion parameters could predict surgical outcome. (3) PET with 2-Deoxy-2-[18F]fluoroglucose ([18F]FDG ) showed a global reduction of glucose metabolism without a specific cortical pattern and a hypometabolism in basal ganglia; [18F]FDG PET may identify a coexisting neurodegenerative disease, helping in patient selection for surgery; postsurgery increase in glucose metabolism was associated with clinical improvement. (4) Dopaminergic PET imaging showed a postsynaptic D2 receptor reduction and striatal upregulation of D2 receptor after treatment, associated with clinical improvement. Overall, PET imaging could be a useful tool in iNPH diagnoses and treatment response.


2003 ◽  
Vol 88 (3) ◽  
pp. 1271-1279 ◽  
Author(s):  
Katherine V. Williams ◽  
Alessandra Bertoldo ◽  
Bruno Mattioni ◽  
Julie C. Price ◽  
Claudio Cobelli ◽  
...  

2006 ◽  
Vol 91 (9) ◽  
pp. 3394-3403 ◽  
Author(s):  
L. Slimani ◽  
V. Oikonen ◽  
K. Hällsten ◽  
N. Savisto ◽  
J. Knuuti ◽  
...  

Abstract Context/Objective: Insulin resistance in obese subjects results in the impaired disposal of glucose by skeletal muscle. The current study examined the effects of insulin and/or exercise on glucose transport and phosphorylation in skeletal muscle and the influence of obesity on these processes. Subjects/Methods: Seven obese and 12 lean men underwent positron emission tomography with 2-deoxy-2-[18F]fluoro-d-glucose in resting and isometrically exercising skeletal muscle during normoglycemic hyperinsulinemia. Data were analyzed by two-tissue compartmental modeling. Perfusion and oxidative capacity were measured during insulin stimulation by [15O]H2O and [15O]O2. Results: Exercise increased glucose fractional uptake (K), inward transport rate (K1), and the k3 parameter, combining transport and intracellular phosphorylation, in lean and obese subjects. In each group, there was no statistically significant difference between plasma flow and K1. At rest, a significant defect in K1 (P = 0.0016), k3 (P = 0.016), and K (P = 0.022) was found in obese subjects. Exercise restored K1, improved but did not normalize K (P = 0.03 vs. lean), and did not ameliorate the more than 60% relative impairment in k3 in obese individuals (P = 0.002 vs. lean). The glucose oxidative potential tended to be reduced by obesity. Conclusions/Interpretation: The study indicates that exercise restores the impairment in insulin-mediated skeletal muscle perfusion and glucose delivery associated with obesity but does not normalize the defect involving the proximal steps regulating glucose disposal in obese individuals. Our data support the use of 2-deoxy-2-[18F]fluoro-d-glucose-positron emission tomography in the dissection between substrate supply and intrinsic tissue metabolism.


1995 ◽  
Vol 269 (6) ◽  
pp. E1000-E1005 ◽  
Author(s):  
M. Raitakari ◽  
M. J. Knuuti ◽  
U. Ruotsalainen ◽  
H. Laine ◽  
P. Makea ◽  
...  

High insulin concentrations increase blood flow in the leg, but it is unknown whether this effect is associated with a change in muscle blood volume. In the present study, we used positron emission tomography combined with inhalation of [15O]carbon monoxide to quantitate the effect of insulin on skeletal muscle blood volume in humans. The reproducibility of the method was determined from two consecutive measurements performed in the basal state in five normal subjects. The coefficient of variation of the repeated measurements was 3.0 +/- 1.8%. In 14 normal subjects [age 35 +/- 3 yr, body mass index 24.9 +/- 1.3 (SE) kg/m2], skeletal muscle blood volume was determined in the femoral region in the basal state and during euglycemic hyperinsulinemia (serum insulin 3,200 +/- 190 pmol/l). The mean muscle blood volume was 3.3 +/- 0.1 ml/0.1 kg muscle in the basal state. Insulin increased muscle blood volume by 9 +/- 2% to 3.6 +/- 0.2 ml/0.1 kg muscle (P < 0.01). The rate of whole body glucose uptake was 53 +/- 6 mumol.kg-1.min-1 and correlated with muscle blood volume during insulin stimulation (r = 0.65, P < 0.02). We conclude that high insulin concentrations exert a true vasodilatory effect in human skeletal muscle.


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