Effects of Gliquidone and Glibenclamide on Metabolic Response and Insulin Receptor Interaction in Monocytes from Patients with Type 2 Diabetes Mellitus
- 作者：Ciccarone ; Annamaria ; Cecchetti ; Paolo ; Orsini ; Paolo ; Di Cianni ; Graziano ; Coppini ; Alessandro ; et. al.
- 关键词：gliquidone ; glibenclamide ; metabolic control ; insulin processing ; insulin receptor
- 刊名：Current Therapeutic Research
- 出版年：1999
- 期刊代码：75_0011393x
- 类别：med
- 出版时间：June, 1999
- 卷：60
- 期：6
- 页码：314-325
- 文件大小：570 K
摘要
In this double-masked study, we compared the effects of 2 sulfonyl-ureas--gliquidone (Gd) and glibenclamide (GI)--on metabolic control and on the interaction of insulin with its receptor. After a 3-week run-in period, 43 untreated patients with type 2 diabetes mellitus, aged 47 to 60 years, were randomly allocated to receive treatment with Gd (n = 22) or Gl (n = 21) for 4 months. Fasting plasma glucose levels decreased similarly in both treatment groups after 4 days and 4 months of treatment. After 4 months of treatment, a superimposable decrease in glycosylated hemoglobin A1c concentrations was seen compared with baseline values (Gd, 7.9 ± 1.4%vs 6.5 ± 0.6%; Gl, 7.6 ± 1.5%vs 6.4 ± 0.9%). No significant changes were noted between treatment groups in body weight or in lipid or leptin levels. Total cell-associated insulin (TCAI) to monocytes increased significantly in the Gd group after 4 days and after 4 months compared with baseline (baseline, 2.13 ± 0.9%; 4 days, 3.14 ± 1.1%; 4 months, 4.33 ± 0.8%; P < 0.01). The insulin internalization index also increased significantly (baseline, 0.60 ± 0.2; 4 days, 0.80 ± 0.1; 4 months, 0.90 ± 0.1; P < 0.01). Finally, insulin degradation increased after 4 days (P < 0.01); however, no further improvement was found after 4 months of therapy (baseline, 68.40 ± 15.0%; 4 days, 84.30 ± 8.0%; 4 months, 86.20 ± 9.0%). In contrast, in the Gl group, after 4 days of treatment no significant changes were noted in TCAI, insulin internalization index, or degradation. After long-term treatment, Gl significantly increased TCAI (baseline, 2.30 ± 0.8%; 4 months, 3.13 ± 0.7%; P < 0.05) and the internalization index (baseline, 0.60 ± 0.2%; 4 months, 0.73 ± 0.1%; P < 0.05), but to a lesser degree than Gd. No effect of Gl on insulin degradation was detected. These data demonstrate that both drugs improve metabolic control in patients with type 2 diabetes mellitus. The difference in their effects on the insulin receptor might be a consequence of the different kinetics of insulin secretion associated with their use. Moreover, only Gd ameliorated insulin degradation, suggesting a direct action of the drug on the degradative pathway of insulin and the existence of different actions of Gd and G1 on this process.