In vivo kinetics of 123 iodine-labelled insulin in skeletal muscle of patients with type 2 diabetes. Effect of metformin.
BACKGROUND
The capillary filtration of albumin (CFA) is often increased in diabetic patients. However, the transcapillary transfer of insulin is considered to be a key stage in insulin action. The aim was to study the in vivo kinetics of 123I-labelled human insulin in the skeletal muscle of type 2 diabetic patients with an increase in CFA and to evaluate the effect of metformin, using a noninvasive method.


METHODS
Ten type 2 diabetic patients and 6 healthy control subjects were investigated. After an i.v injection of 123I-labelled insulin, venous samples were drawn during 75 minutes and radioactivity was counted externally by a gammacamera on the contralateral forearm before, during and after venous compression. The changes in the serum percentages of bound and free 123I were followed during the entire test and the forearm iodine bound to insulin was estimated by multiplying the forearm counted radioactivity by the serum percentage of bound iodine at the same time.


RESULTS
In the diabetic patients the maximal increase in the forearm iodine bound to insulin during venous compression was lower (p=0.06), and 10 minutes after removal of venous compression the forearm retention of labelled insulin was significantly lower (p<0.0005) than in controls. After one month of metformin treatment, retention of labelled insulin significantly increased (p<0.001) but was still significantly lower than in the controls (p<0.001).


CONCLUSIONS
The in vivo kinetics of (123) I-labelled insulin procedure allows the study of skeletal muscle metabolism provided venous compression is exerted. In type 2 diabetic patients a reduction of insulin transfer from capillary to tissue despite an increase in CFA, and a reduction of the time spent by insulin in the tissues contribute to insulin resistance. The latter disorder may be improved by metformin.
Valensi
P
P
Laboratory of Nutrition and Metabolic diseases, Jean Verdier Hospital, Paris-Nord University, Bondy, France. paul.valensi@jvr.ap-hop-paris.fr
Behar
A
A
Cohen-Boulakia
F
F
Valensi
J
J
Wiernsperger
N
N
Attali
J R
JR
D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005542:Forearm; D007839:Functional Laterality; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007700:Kinetics; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D014018:Tissue Distribution
D007004:Hypoglycemic Agents; D007328:Insulin; D007457:Iodine Radioisotopes; D008687:Metformin