Mandarino L J, Gerich J E
Diabetes Care. 1984 May-Jun;7 Suppl 1:89-99.
To determine whether long-term sulfonylurea therapy ameliorates glucose homeostasis in patients with NIDDM predominantly by improving insulin secretion or by improving insulin action, we evaluated changes in fasting plasma glucose concentrations, intravenous glucose tolerance, glucose-stimulated insulin secretion, facilitation of glucose disposal by exogenous insulin, and erythrocyte insulin receptor binding before and after prolonged (congruent to 4 mo) administration of tolazamide to 18 patients with NIDDM. Before tolazamide administration, 15 patients had decreased insulin secretion (50 +/- 31 vs 577 +/- 176 microU/ml X 10 min in nondiabetic subjects, P less than 0.05) and insulin resistance (Km 166 +/- 31 vs 58 +/- 3 microU/ml in nondiabetic subjects, P less than 0.05; Vmax 7.3 +/- 0.6 vs 9.8 +/- 0.2 mg/kg/min in nondiabetic subjects, P less than 0.05), whereas the other three patients had comparably impaired insulin secretion (56 +/- 52 microU/ml X min) but were not insulin resistant (Km 70 +/- 6 microU/ml; Vmax 10.8 +/- 0.6 mg/kg/min). The insulin-resistant patients had fasting hyperinsulinemia (19 +/- 4 vs 11 +/- 1 microU/ml in nondiabetic subjects, P less than 0.05), decreased erythrocyte insulin receptor binding (4.8 +/- 0.4 vs 5.8 +/- 0.3%/1.6 X 10(9) cells in nondiabetic subjects, P less than 0.05), and impairment in both insulin-induced suppression of glucose production (Km 97 +/- 31 vs 21 +/- 7 microU/ml in nondiabetic subjects, P less than 0.05), and insulin-induced stimulation of glucose utilization (Km and Vmax 176 +/- 29 microU/ml and 5.8 +/- 0.7 mg/kg/min vs 50 +/- 2 microU/ml and 9.1 +/- 0.6 mg/kg/min in nondiabetic subjects, both P less than 0.05). The nonresistant patients were not hyperinsulinemic (12 +/- micU/ml), had normal insulin receptor binding (5.9 +/- 0.5%/1.6 X 10(9) cells), and were less hyperglycemic than the insulin-resistant patients (128 +/- 11 vs 181 +/- 12 mg/dl, P less than 0.05). After tolazamide administration, both the early phase of glucose-induced insulin secretion (56 +/- 52 vs 141 +/- 68 microU/ml . 10 min) and insulin binding (5.9 +/- 0.5 vs 7.0 +/- 0.5%/1.6 X 10(9) cells) increased in all three nonresistant patients, but there was no consistent improvement in fasting hyperglycemia (128 +/- 11 vs 130 +/- 24 mg/dl), intravenous glucose tolerance (Kivgtt 0.77 +/- 0.18 vs 0.89 +/- 0.29%/min), or facilitation of glucose disposal by insulin (Km 70 +/- 5 vs 64 +/- 5 microU/ml; Vmax 10.8 +/- 0.6 vs 10.1 +/- 0.2 mg/kg/min).(ABSTRACT TRUNCATED AT 400 WORDS)
为了确定长期磺脲类药物治疗改善非胰岛素依赖型糖尿病（NIDDM）患者的葡萄糖稳态主要是通过改善胰岛素分泌还是改善胰岛素作用，我们评估了18例NIDDM患者在长期（约4个月）服用甲苯磺丁脲前后空腹血糖浓度、静脉葡萄糖耐量、葡萄糖刺激的胰岛素分泌、外源性胰岛素促进葡萄糖处置以及红细胞胰岛素受体结合的变化。在服用甲苯磺丁脲之前，15例患者胰岛素分泌减少（非糖尿病受试者为577±176微单位/毫升×10分钟，而这些患者为50±31微单位/毫升×10分钟，P<0.05）且存在胰岛素抵抗（非糖尿病受试者Km为58±3微单位/毫升，这些患者为166±31微单位/毫升，P<0.05；非糖尿病受试者Vmax为9.8±0.2毫克/千克/分钟，这些患者为7.3±0.6毫克/千克/分钟，P<0.05），而另外3例患者胰岛素分泌受损程度相当（56±52微单位/毫升·分钟）但不存在胰岛素抵抗（Km为70±6微单位/毫升；Vmax为10.8±0.6毫克/千克/分钟）。胰岛素抵抗患者存在空腹高胰岛素血症（非糖尿病受试者为11±1微单位/毫升，这些患者为19±4微单位/毫升，P<0.05），红细胞胰岛素受体结合减少（非糖尿病受试者为5.8±0.3%/1.6×10⁹细胞，这些患者为4.8±0.4%/1.6×10⁹细胞，P<0.05），并且在胰岛素诱导的葡萄糖生成抑制（非糖尿病受试者Km为21±7微单位/毫升，这些患者为97±31微单位/毫升，P<0.05）以及胰岛素诱导的葡萄糖利用刺激（非糖尿病受试者Km和Vmax分别为50±2微单位/毫升和9.1±0.6毫克/千克/分钟，这些患者为176±29微单位/毫升和5.8±0.7毫克/千克/分钟，两者P<0.05）方面均受损。无抵抗患者不存在高胰岛素血症（12±微单位/毫升），胰岛素受体结合正常（5.9±0.5%/1.6×10⁹细胞），且血糖水平低于胰岛素抵抗患者（128±11与181±12毫克/分升，P<0.05）。服用甲苯磺丁脲后，所有3例无抵抗患者的葡萄糖诱导胰岛素分泌早期阶段（56±52与141±68微单位/毫升·10分钟）和胰岛素结合（5.9±0.5与7.0±0.5%/1.6×10⁹细胞）均增加，但空腹高血糖（128±11与130±24毫克/分升）、静脉葡萄糖耐量（Kivgtt为0.77±0.18与0.89±0.29%/分钟）或胰岛素促进葡萄糖处置（Km为70±5与64±5微单位/毫升；Vmax为10.8±0.6与10.1±0.2毫克/千克/分钟）方面没有持续改善。（摘要截断于400字）
