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

被引:49
作者
Juhl, CB
Hollingdal, M
Porksen, N
Prange, Å
Lönnqvist, F
Schmitz, O
机构
[1] Aarhus Univ Hosp, Med Dept Endocrinol & Diabet M, DK-8000 Aarhus C, Denmark
[2] Kolding Sygehus, Dept Med, DK-6000 Kolding, Denmark
[3] Huddinge Univ Hosp, Karolinska Inst, Ctr Metab & Endocrinol, S-17177 Stockholm, Sweden
[4] Aarhus Univ, Inst Clin Pharmacol, Aarhus, Denmark
关键词
D O I
10.1210/jc.2002-021181
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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收藏
页码:3794 / 3800
页数:7
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