In vivo assessment of cardiac insulin resistance by nuclear probes using an iodinated tracer of glucose transport.
OBJECTIVE
Insulin resistance, implying depressed cellular sensitivity to insulin, is a risk factor for type 2 diabetes and cardiovascular disease. This study is the first step towards the development of a technique of insulin resistance measurement in humans with a new tracer of glucose transport, [(123)I]6-deoxy-6-iodo-D-glucose (6DIG).


METHODS
We investigated 6DIG kinetics in anaesthetised control rats and in three models of insulin-resistant rats: fructose fed, Zucker and ZDF. The study of myocardial 6DIG activity was performed under two conditions: first, 6DIG was injected under the baseline condition and then it was injected after a bolus injection of insulin. After each injection, radioactivity was measured over 45 min by external detection via NaI probes, in the heart and blood. A tri-compartment model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the heart.


RESULTS
These coefficients were significantly increased with insulin in control rats and did not change significantly in insulin-resistant rats. The ratio of the coefficient obtained under insulin to that obtained under basal conditions gave an index of cardiac insulin resistance for each animal. The mean values of these ratios were significantly lower in insulin-resistant than in control rats: 1.16 +/- 0.06 vs 2.28 +/- 0.18 (p < 0.001) for the fructose-fed group, 0.92 +/- 0.05 vs 1.62 +/- 0.25 (p < 0.01) for the Zucker group and 1.34 +/- 0.06 vs 2.01 +/- 0.26 (p < 0.05) for the ZDF group.


CONCLUSIONS
These results show that 6DIG could be a useful tracer to image cardiac insulin resistance.
Briat
Arnaud
A
INSERM, E0340, Radiopharmaceutiques Biocliniques, Grenoble 38000, France.
Slimani
Lotfi
L
Perret
Pascale
P
Villemain
Danièle
D
Halimi
Serge
S
Demongeot
Jacques
J
Fagret
Daniel
D
Ghezzi
Catherine
C
D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000000981:diagnostic imaging; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007333:Insulin Resistance / Q000502:physiology*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008297:Male; D015336:Molecular Probe Techniques; D009206:Myocardium / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker
C105926:6-deoxy-6-iodoglucose; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D003847:Deoxyglucose; D005947:Glucose