Influence of rosiglitazone treatment on β-cell function in type 2 diabetes:: Evidence of an increased ability of glucose to entrain high-frequency insulin pulsatility
Influence of rosiglitazone treatment on β-cell function in type 2 diabetes:: Evidence of an increased ability of glucose to entrain high-frequency insulin pulsatility
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DOI：
10.1210/jc.2002-021181
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发表时间：
2003-08-01
影响因子：
5.8
通讯作者：
Schmitz, O
中科院分区：
文献类型：
--
作者：
Juhl, CB;Hollingdal, M;Schmitz, O
噻唑烷二酮具有公认的胰岛素增敏作用。它们对胰岛素分泌的影响尚不清楚。因此，我们试图确定噻唑烷二酮（罗格列酮）对β细胞功能的潜在影响。20名2型糖尿病患者随机接受罗格列酮（rosi） 4毫克，每日两次或安慰剂（pla），为期13周。在治疗前和治疗期结束时，患者接受静脉糖耐量试验（0.3 g/kg），高血糖（15 mmol/l）钳夹和精氨酸刺激（5 g），评估基线高频胰岛素搏动性和葡萄糖携带胰岛素搏动性（6 mg/kg）。（每10分钟一次），高胰岛素正糖钳。罗格列酮使空腹血糖降低（pla, 8.2 +/- 2.1 vs 8.8 +/- 2.6 mmol/l; rosi, 8.6 +/- 7.1 vs 7.1 +/- 1.2 mmol/l, P < 0.01），胰岛素敏感性升高（M值：pla， 5.3 +/- 1.8 vs 5.4 +/- 1.6 mg/kg.min; rosi, 5.9 +/- 2.2 vs 7.4 +/- 1.3 mg/kg.min, P = 0.05）。一期胰岛素分泌和胰岛素分泌能力未受影响。经谱功率分析，葡萄糖携带的胰岛素分泌增加（P = 0.05）。综上所述，罗格列酮治疗3个月对2型糖尿病患者胰岛素分泌本身没有影响。改善葡萄糖携带的高频胰岛素搏动表明β细胞在生理范围内感知和响应葡萄糖变化的能力增强。
Thiazolidinediones have well-established insulin-sensitizing effects. Their impact on insulin secretion is less clarified. Consequently, we sought to determine potential effects of a thiazolidinedione (rosiglitazone) on the beta-cell function. Twenty type 2 diabetic individuals were randomized to receive rosiglitazone (rosi) 4 mg twice daily or placebo (pla) for 13 wk. Before treatment and at the end of the treatment period, the patients underwent an iv glucose tolerance test (0.3 g/kg), a hyperglycemic (15 mmol/liter) clamp with arginine (5 g) stimulation, assessment of baseline high-frequency insulin pulsatility, and glucose-entrained insulin pulsatility (6 mg/kg.min every 10 min), and a hyperinsulinemic euglycemic clamp. Fasting plasma glucose was reduced (pla, 8.2 +/- 2.1 vs. 8.8 +/- 2.6 mmol/liter; rosi, 8.6 +/- 7.1 vs. 7.1 +/- 1.2 mmol/liter; P < 0.01), and insulin sensitivity was increased by rosiglitazone treatment (M value: pla, 5.3 +/- 1.8 vs. 5.4 +/- 1.6 mg/kg.min; rosi, 5.9 +/- 2.2 vs. 7.4 +/- 1.3 mg/kg.min; P = 0.05). First-phase insulin secretion and insulin secretory capacity were unaffected. Glucose-entrained insulin secretion was increased as assessed by spectral power analysis (P = 0.05). In conclusion, rosiglitazone treatment for 3 months in type 2 diabetic patients exerts no action on insulin secretion per se. Improved glucose-entrained high-frequency insulin pulsatility suggests an increased ability of the beta-cell to sense and respond to glucose changes within the physiological range.