Insulin activation of insulin receptor kinase in erythrocytes is not altered in non-insulin-dependent diabetes and not influenced by hyperglycemia

Recent studies suggest that high glucose concentrations impair insulin rece ptor phosphorylation and kinase activation in certain cell models. To exami ne whether such an effect of glucose call also be demonstrated in vivo, ins ulin receptor kinase activation was studied in erythrocytes from 11 patient s with non-insulin-dependent diabetes (NIDDM), before and after reduction o f hyperglycemia (from 14.6 +/- 1.6 to 6.6 +/- 0.5 nmol/l fasting plasma glu cose within 8.6 +/- 0.6 days). For the measurement of receptor kinase activ ation, cells were incubated with insulin (0-400 nmol/l), solubilized and in sulin receptors immobilized to microwells coated with antiinsulin receptor antibody. Kinase activity towards insulin receptor substrate-1 and insulin binding were then measured in these wells. Kinase activities (expressed as amol phosphate transferred per min and per fmol insulin binding activity) w ere similar before (2.4 +/- 0.4 and 32.2 +/- 2.0 amol/min per fmol with 0 a nd 400 nmol/l insulin, respectively) and after improvement of metabolic con trol (2.4 +/- 0.5 and 32.0 +/- 2.3 amol/min per fmol with 0 and 400 nmol/l insulin, respectively). Moreover, activities were also similar in 22 hyperg lycemic patients with NIDDM (2.1 +/- 0.3 and 35.1 +/- 1.4 amol/min per fmol with 0 and 400 nmol/l insulin, respectively) compared with those in 21 non -diabetic control individuals (2.1 +/- 0.3 and 34.2 +/- 1.2 amol/min per fm ol with 0 and 400 nmol/l insulin, respectively). We conclude that insulin a ctivation of erythrocyte insulin receptor kinase is not impaired in NIDDM a nd is not influenced by hyperglycemia.