Assessment of insulin resistance in fructose-fed rats with 125I-6-deoxy-6-iodo-D-glucose, a new tracer of glucose transport.
OBJECTIVE
Insulin resistance, characterised by an insulin-stimulated glucose transport defect, is an important feature of the pre-diabetic state that has been observed in numerous pathological disorders. The purpose of this study was to assess variations in glucose transport in rats using (125)I-6-deoxy-6-iodo-D-glucose (6DIG), a new tracer of glucose transport proposed as an imaging tool to assess insulin resistance in vivo.


METHODS
Two protocols were performed, a hyperinsulinaemic-euglycaemic clamp and a normoinsulinaemic-normoglycaemic protocol, in awake control and insulin-resistant fructose-fed rats. The tracer was injected at steady state, and activity in 11 tissues and the blood was assessed ex vivo at several time points. A multicompartmental mathematical model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the organs.


RESULTS
Insulin sensitivity of fructose-fed rats, estimated by the glucose infusion rate, was reduced by 40% compared with control rats. At steady state, 6DIG uptake was significantly stimulated by insulin in insulin-sensitive tissues of control rats (basal versus insulin: diaphragm, p < 0.01; muscle, p<0.05; heart, p<0.001), whereas insulin did not stimulate 6DIG uptake in insulin-resistant fructose-fed rats. Moreover, in these tissues, the fractional transfer coefficients of entrance were significantly increased with insulin in control rats (basal vs insulin: diaphragm, p<0.001; muscle, p<0.001; heart, p<0.01) whereas no significant changes were observed in fructose-fed rats.


CONCLUSIONS
This study sets the stage for the future use of 6DIG as a non-invasive means for the evaluation of insulin resistance by nuclear imaging.
Perret
Pascale
P
INSERM, E340, 38000 Grenoble,, France. pascale.perret@ujf-grenoble.fr.|Univ Grenoble, 38000 Grenoble,, France. pascale.perret@ujf-grenoble.fr.
Slimani
Lotfi
L
INSERM, E340, 38000 Grenoble,, France.|Univ Grenoble, 38000 Grenoble,, France.
Briat
Arnaud
A
INSERM, E340, 38000 Grenoble,, France.|Univ Grenoble, 38000 Grenoble,, France.
Villemain
Danièle
D
INSERM, E340, 38000 Grenoble,, France.|Univ Grenoble, 38000 Grenoble,, France.
Halimi
Serge
S
CHRU Grenoble, Hôpital Michallon, Service de Diabétologie, , 38000 Grenoble,, France.
Demongeot
Jacques
J
Univ Grenoble, 38000 Grenoble,, France.|CNRS, UMR 5525, 38000 Grenoble, , France.
Fagret
Daniel
D
INSERM, E340, 38000 Grenoble,, France.|Univ Grenoble, 38000 Grenoble,, France.
Ghezzi
Catherine
C
INSERM, E340, 38000 Grenoble,, France.|Univ Grenoble, 38000 Grenoble,, France.
D000818:Animals; D001692:Biological Transport; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003952:Diagnostic Imaging / Q000379:methods; D005632:Fructose / Q000378:metabolism / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D008962:Models, Theoretical; D051381:Rats; D017208:Rats, Wistar
C105926:6-deoxy-6-iodoglucose; D007328:Insulin; D007457:Iodine Radioisotopes; D005632:Fructose; D003847:Deoxyglucose; D005947:Glucose