Assessment of insulin sensitivity in vivo in control and diabetic mice with a radioactive tracer of glucose transport: [125I]-6-deoxy-6-iodo-D-glucose.
BACKGROUND
Impairment of insulin-stimulated glucose transport is a characteristic of type 2 diabetes. A radioactive glucose analogue has been synthesized: [(125)I]-6-deoxy-6-iodo-D-glucose. Its biological behaviour in vitro is similar to that of 3-O-methyl-D-glucose, the reference tracer of glucose transport. The aim of the present study was to determine the ability of [(125)I]-6-deoxy-6-iodo-D-glucose to evaluate variations in glucose transport in vivo.


METHODS
Biodistributions of [(125)I]-6-deoxy-6-iodo-D-glucose were performed with or without exogenous insulin (iv injection of 1.5 IU/kg) in db/+ non-diabetic control mice and in db/db type 2 diabetic mice, exhibiting a severe insulin resistance characterized by a lack of increase in glucose uptake in response to insulin.


RESULTS
In db/+ mice, insulin increased [(125)I]-6-deoxy-6-iodo-D-glucose transport by 30% in most insulin-sensitive tissues (heart, diaphragm and skeletal muscle, p < 0.05) and had no effect in other organs. In db/db mice, [(125)I]-6-deoxy-6-iodo-D-glucose transport in these organs was not modified by insulin.


CONCLUSIONS
[(125)I]-6-deoxy-6-iodo-D-glucose is able to trace in vivo an increase in glucose transport with insulin in non-diabetic mice and a defect of glucose transport in type 2 diabetic mice. It is the first time that an iodinated analogue of glucose has shown such promising results after in vivo injection. The use of this tracer to assess glucose transport in vivo in humans via nuclear imaging warrants further investigation.
Perret
P
P
Radiopharmaceutiques Biocliniques, INSERM E 0340, Faculté de Médecine de Grenoble, Domaine de la Merci, La Tronche, France.
Ghezzi
C
C
Mathieu
J P
JP
Morin
C
C
Fagret
D
D
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D007457:Iodine Radioisotopes; D051379:Mice; D008810:Mice, Inbred C57BL; D011865:Radioisotope Dilution Technique; D012016:Reference Values; D014018:Tissue Distribution
C105926:6-deoxy-6-iodoglucose; D007457:Iodine Radioisotopes; D003847:Deoxyglucose; D005947:Glucose