Insulin receptor binding and insulin-mediated glucose uptake in type-II-diabetics

A 5-hour insulin clamp was performed in 7 normal subjects (N) and 6 type-II-diabetics. After a 10-min-priming insulin infusion, a constant infusion of 1.813 micrograms/m2 s.a./min was given to all subjects. Glycemia was kept at fasting levels by a variable glucose infusion. Under these conditions the amount of metabolized glucose (M) has been calculated and served as a measure of insulin-stimulated glucose disposal. M differed markedly between N (35.6 +/- 3.11 mumol glucose/kg b.w./min and diabetics (17.8 +/- 1.17 mumol glucose/kg b.w./min; p less than 0.01) indicating a diminished insulin sensitivity in the latter group. However, M increased slightly but significantly until the end of the study in both groups. Under fasting conditions the mean percent 125I-insulin specifically bound to 3.5 X 10(9) erythrocytes/ml at tracer concentrations was 12 +/- 1.2% and 8.9 +/- 0.9% in N and diabetics, respectively. During insulin infusion specific insulin binding decreased significantly in both groups by 34% and 41%. Thus, the downregulation of insulin binding was similar in both groups and was due to changes in receptor affinity. Assuming that insulin binding to red blood cells mimic that to target cells we conclude that the cause of reduced glucose utilization in type-II-diabetes lies mainly in changes of postreceptor events rather than in receptor binding.