Rosiglitazone reduces glucose-stimulated insulin secretion rate and increases insulin clearance in nondiabetic, insulin-resistant individuals
Rosiglitazone reduces glucose-stimulated insulin secretion rate and increases insulin clearance in nondiabetic, insulin-resistant individuals
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DOI：
10.2337/diabetes.54.8.2447
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发表时间：
2005-08-01
期刊：
影响因子：
7.7
通讯作者：
Reaven, GM
中科院分区：
文献类型：
--
作者：
Kim, SH;Abbasi, F;Reaven, GM
代偿性高胰岛素血症允许胰岛素抵抗个体维持正常的葡萄糖耐量，与葡萄糖刺激的胰岛素分泌率（GS-ISR）剂量反应曲线左移和胰岛素代谢清除率（I-MCR）降低相关。为了观察这些变化是否会随着胰岛素敏感性的改善而逆转，14名非糖尿病胰岛素抵抗受试者接受罗格列酮治疗12周（每天4 mg，持续4周，然后每天8 mg，持续8周）。通过在胰岛素抑制试验期间测量稳态血糖浓度来定量胰岛素介导的葡萄糖摄取。GS-ISR和I-MCR在240分钟分级静脉输注葡萄糖期间测定。在胰岛素抑制试验期间还计算了I-MCR。罗格列酮治疗后，胰岛素敏感性改善，稳态血糖显著下降（平均值± SE从13.5 ± 0.62 mmol/l降至9.8 ± 1.02 mmol/l，P < 0.001）。作为响应，积分GS-ISR降低21%（P < 0.001），剂量-响应曲线右移。胰岛素抑制试验期间计算的I-MCR增加34%（P = 0.008），分级葡萄糖输注期间增加21%（P = 0.03）。总之，罗格列酮治疗的非糖尿病胰岛素抵抗个体的胰岛素敏感性增强与GS-ISR剂量-反应曲线右移和I-MCR增加相关。
Compensatory hyperinsulinemia permitting insulin-resistant individuals to maintain normal glucose tolerance is associated with a left shift in the glucose-stimulated insulin secretion rate (GS-ISR) dose-response curve and decrease in the insulin metabolic clearance rate (I-MCR). To see whether these changes would reverse with improvement in insulin sensitivity, 14 nondiabetic insulin-resistant subjects received rosiglitazone for 12 weeks (4 mg daily for 4 weeks and then 8 mg daily for 8 weeks). Insulin-mediated glucose uptake was quantified by measuring the steady-state plasma glucose concentration during the insulin suppression test. GS-ISR and I-MCR were determined during a 240-min graded intravenous glucose infusion. I-MCR was also calculated during the insulin suppression test. After rosiglitazone treatment, insulin sensitivity improved with significant fall in steady-state plasma glucose (means +/- SE from 13.5 +/- 0.62 to 9.8 +/- 1.02 mmol/l, P < 0.001). In response, the integrated GS-ISR decreased by 21 % (P < 0.001), with a right shift in the dose-response curve. Calculated I-MCR increased by 34 % (P = 0.008) during the insulin suppression test and by 21 % (P = 0.03) during the graded glucose infusion. In conclusion, enhanced insulin sensitivity in rosiglitazone-treated nondiabetic insulin-resistant individuals was associated with a shift to the right in the GS-ISR dose-response curve and an increase in I-MCR.