Erythrocyte insulin receptor tyrosine kinase activity is increased in glyburide-treated patients with type 2 diabetes in good glycaemic control.
OBJECTIVE
The goal of this study was to test the hypothesis that insulin receptor tyrosine kinase activity of isolated erythrocytes would be greater in glyburide-treated patients with type 2 diabetes in good glycaemic control (n = 13) than in untreated patients (n = 12) with significant fasting hyperglycaemia.


METHODS
The two groups were similar in age, sex distribution, and body mass index. By selection, glyburide-treated patients had significantly (p < 0.001) lower (mean +/- s.e.m.) fasting glucose (6.9+/-0.4 vs. 13.9+/-0.8 mmol/l) and HbA(IC) (7.4+/-0.2 vs. 11.8+/-0.9%) concentrations. In addition, insulin-stimulated tyrosine kinase activity was increased in erythrocytes from glyburide -treated patients (p < 0.01).


RESULTS
Although insulin receptor number was similar in solubilized erythrocytes from the two groups, tyrosine kinase activity per insulin receptor was significantly (p < 0.02) greater in erythrocytes from glyburide-treated patients with type 2 diabetes.


CONCLUSIONS
These findings are quite similar to previously published data in metformin-treated patients. As such, it is suggested that decreases in insulin receptor tyrosine kinase activity may contribute to the loss of insulin sensitivity in hyperglycaemic subjects (glucotoxicity), and that an improvement in glycaemic control, irrespective of how it is achieved, will help rectify this abnormality.
Santos
R F
RF
Laboratório de Carboidratos e Radioimunoensaio LIM-18, School of Medicine, University of São Paulo, Brazil.
Nomizo
R
R
Oliveira
E
E
Ursich
M
M
Wajchenberg
B
B
Reaven
G M
GM
Azhar
S
S
D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy* / Q000201:enzymology; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005905:Glyburide / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011972:Receptor, Insulin / Q000097:blood* / Q000187:drug effects
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011972:Receptor, Insulin; D005905:Glyburide