Santos R F, Nomizo R, Oliveira E, Ursich M, Wajchenberg B, Reaven G M, Azhar S
Laboratório de Carboidratos e Radioimunoensaio LIM-18, School of Medicine, University of São Paulo, Brazil.
Diabetes Obes Metab. 2000 Aug;2(4):237-41. doi: 10.1046/j.1463-1326.2000.00091.x.
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.
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).
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.
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.
本研究的目的是检验以下假设:与未治疗的空腹血糖显著升高的患者(n = 12)相比,接受格列本脲治疗且血糖控制良好的2型糖尿病患者(n = 13)分离的红细胞中胰岛素受体酪氨酸激酶活性更高。
两组在年龄、性别分布和体重指数方面相似。经选择,接受格列本脲治疗的患者空腹血糖(6.9±0.4对13.9±0.8 mmol/l)和糖化血红蛋白(HbA1c)浓度(7.4±0.2对11.8±0.9%)显著更低(p < 0.001)。此外,格列本脲治疗患者红细胞中胰岛素刺激的酪氨酸激酶活性增加(p < 0.01)。
虽然两组溶解红细胞中的胰岛素受体数量相似,但2型糖尿病格列本脲治疗患者红细胞中每个胰岛素受体的酪氨酸激酶活性显著更高(p < 0.02)。
这些发现与先前发表的二甲双胍治疗患者的数据非常相似。因此,提示胰岛素受体酪氨酸激酶活性降低可能导致高血糖受试者胰岛素敏感性丧失(糖毒性),且无论血糖控制如何实现,血糖控制的改善将有助于纠正这种异常。