Impact of incretin hormones on β-cell function in subjects with normal or impaired glucose tolerance
Impact of incretin hormones on β-cell function in subjects with normal or impaired glucose tolerance
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DOI：
10.1152/ajpendo.00571.2005
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发表时间：
2006-12-01
影响因子：
5.1
通讯作者：
Ferrannini, Ele
中科院分区：
文献类型：
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作者：
Muscelli, Elza;Mari, Andrea;Ferrannini, Ele
肠岛轴影响β细胞功能的机制尚未得到详细研究。我们对正常（NGT, n = 11）或糖耐量受损（IGT, n = 10）的受试者进行口服和等糖静脉（IV）葡萄糖给药，使用c肽反褶积计算胰岛素分泌率，并用数学模型量化β细胞功能。肠促胰岛素效应被认为是口服与静脉注射反应的比率。在NGT中，肠促胰岛素介导的胰岛素释放[口服糖耐量试验(OGTT)/IV比值= 1.59 +/- 0.18,P = 0.004]达18 +/- 2 nmol/m(2)（口服应答的32 +/- 4%），其时间过程与总胰岛素分泌相符。口服葡萄糖的β细胞葡萄糖敏感性（OGTT/IV比值= 1.52 +/- 0.26,P = 0.02）、速率敏感性（对葡萄糖变化率的反应，OGTT/IV比值= 2.22 +/- 0.37,P = 0.06）和葡萄糖非依赖性增强均显著高于静脉注射葡萄糖。在IGT中，β细胞葡萄糖敏感性（75 +/- 14 vs 156 +/- 28 pmol）和增强作用在OGTT上受到损害（NGT中心dot min（-1）中心dot m（-2）中心dot mM(-1), P = 0.01）。在血浆胰高血糖素样肽1和葡萄糖依赖的促胰岛素多肽反应、胰岛素总分泌和β细胞葡萄糖敏感性增强方面，肠促胰岛素效应与NGT无显著差异（OGTT/IV比值= 1.73 +/- 0.24,P = NS vs. NGT）。然而，肠促胰岛素介导的胰岛素分泌和增强的时间过程发生了改变，葡萄糖诱导的刺激和肠促胰岛素介导的刺激占主导地位。我们得出结论，在生理环境下，肠促胰岛素介导的胰岛素分泌刺激是由于β细胞功能的所有动态方面的增强，特别是β细胞的葡萄糖敏感性。在IGT中，β细胞功能固有受损，而肠促胰岛素的作用仅部分受到影响。
The mechanisms by which the enteroinsular axis influences beta-cell function have not been investigated in detail. We performed oral and isoglycemic intravenous (IV) glucose administration in subjects with normal (NGT; n = 11) or impaired glucose tolerance (IGT; n = 10), using C-peptide deconvolution to calculate insulin secretion rates and mathematical modeling to quantitate beta-cell function. The incretin effect was taken to be the ratio of oral to IV responses. In NGT, incretin-mediated insulin release [oral glucose tolerance test (OGTT)/IV ratio = 1.59 +/- 0.18, P = 0.004] amounted to 18 +/- 2 nmol/m(2) (32 +/- 4% of oral response), and its time course matched that of total insulin secretion. The beta-cell glucose sensitivity (OGTT/IV ratio = 1.52 +/- 0.26, P = 0.02), rate sensitivity ( response to glucose rate of change, OGTT/IV ratio = 2.22 +/- 0.37, P = 0.06), and glucose-independent potentiation were markedly higher with oral than IV glucose. In IGT, beta-cell glucose sensitivity (75 +/- 14 vs. 156 +/- 28 pmol center dot min(-1) center dot m(-2) center dot mM(-1) of NGT, P = 0.01) and potentiation were impaired on the OGTT. The incretin effect was not significantly different from NGT in terms of plasma glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide responses, total insulin secretion, and enhancement of beta-cell glucose sensitivity (OGTT/IV ratio = 1.73 +/- 0.24, P = NS vs. NGT). However, the time courses of incretin-mediated insulin secretion and potentiation were altered, with a predominance of glucose-induced vs. incretin-mediated stimulation. We conclude that, under physiological circumstances, incretin-mediated stimulation of insulin secretion results from an enhancement of all dynamic aspects of beta-cell function, particularly beta-cell glucose sensitivity. In IGT, beta-cell function is inherently impaired, whereas the incretin effect is only partially affected.