Increased β-Cell Secretory Capacity as Mechanism for Islet Adaptation to Nicotinic Acid-Induced Insulin Resistance
Increased β-Cell Secretory Capacity as Mechanism for Islet Adaptation to Nicotinic Acid-Induced Insulin Resistance
复制标题
β细胞分泌能力增加是胰岛适应烟酸诱导的胰岛素抵抗的机制
作者：
S. Kahn;J. C. Beard;M. Schwartz;W. Ward;Han Lun Ding;R. Bergman;G. Taborsky;D. Porte
为了确定是否长期烟酸（NA）管理产生胰岛素抵抗，如果是这样的话，正常的胰岛如何适应长期的胰岛素抵抗，我们给11名正常男性递增剂量的NA 2周，结束在2克/天。胰岛素敏感性测定采用Bergman最小模型。通过测量三种葡萄糖水平下精氨酸对胰岛素（AIR）和胰高血糖素（AGR）的急性反应来评价胰岛功能。通过胰岛素敏感性指数（S1）从6.72 ± 0.77显著下降至2.47 ± 0.36 × 10−5 min−1/pM，证实并量化了胰岛素抵抗（P < .0001），并导致基础免疫反应性胰岛素水平加倍（从75 ± 7至157 ± 21 pM，P <0.001），空腹血糖无变化（5.5 ± 0.1 vs 5.7 ± 0.1 mM）。胰岛素原水平也增加（从9 ± 1至15 ± 2 pM，P <0.005），但胰岛素原与免疫反应性胰岛素的比例没有变化（12.7 ± 1.9 vs. 10.3 ± 1.9%）。β-细胞变化的特征是在空腹血糖水平下，葡萄糖的AIR增加（从548 ± 157到829 ± 157 pM，P <0.005），精氨酸的AIR增加（从431 ± 54到788 ± 164 pM，P <0.05）。在最大高血糖水平下，AIR对精氨酸的反应代表β细胞的分泌能力，并且随着NA的施用而增加（从2062 ± 267至2630 ± 363 pM，P <0.05）。从AIR到精氨酸，可以计算给出一半最大AIR到精氨酸的葡萄糖水平的估计值。该测量值未增加（10.0 ± 0.5 vs. 9.6 ± 0.9 mM）。在NA给药期间，在所有葡萄糖水平下，对精氨酸的AGR均降低。因此，胰岛适应NA诱导的长期胰岛素抵抗。这种适应包括胰岛素分泌增加和胰高血糖素分泌减少的组合。胰岛素分泌的变化完全可以用β细胞分泌能力的增加来解释。
To determine whether prolonged nicotinic acid (NA) administration produces insulin resistance and, if so, how the normal pancreatic islet adapts to prolonged insulin resistance, we administered incremental doses of NA to 11 normal men for 2 wk, ending at 2 g/day. Insulin sensitivity was measured with Bergman's minimal model. Islet function was evaluated by measurement of acute insulin (AIR) and glucagon (AGR) responses to arginine at three glucose levels. Insulin resistance was demonstrated and quantified by a marked drop in the insulin sensitivity index (S1) from 6.72 ± 0.77 to 2.47 ± 0.36 × 10−5 min−1/pM (P < .0001) and resulted in a doubling of basal immunoreactive insulin levels (from 75 ± 7 to 157 ± 21 pM, P < .001) with no change in fasting glucose (5.5 ± 0.1 vs. 5.7 ± 0.1 mM). Proinsulin levels also increased (from 9 ± 1 to 15 ± 2 pM, P < .005), but the ratio of proinsulin to immunoreactive insulin did not change (12.7 ± 1.9 vs. 10.3 ± 1.9%). β-Cell changes were characterized by increases in the AIR to glucose (from 548 ± 157 to 829 ± 157 pM, P < .005) and in the AIR to arginine at the fasting glucose level (from 431 ± 54 to 788 ± 164 pM, P < .05). At the maximal hyperglycemia level the AIR to arginine represents β-cell secretory capacity, and this increased with administration of NA (from 2062 ± 267 to 2630 ± 363 pM, P < .05). From the AIRs to arginine an estimate of the glucose level giving half-maximal AIR to arginine can be calculated. This measure did not increase (10.0 ± 0.5 vs. 9.6 ± 0.9 mM). The AGRs to argininewere reduced at all glucose levels during NA administration. Thus, the pancreatic islet adapts to the prolonged insulin resistance induced by NA. This adaptation comprises a combination of increased insulin secretion and reduced glucagon secretion. The changes in insulin secretion can be entirely explained by an increase in the secretory capacity of the β-cell.
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影响因子：
15.9
作者：
ROWE, JW;MINAKER, KL;FLIER, JS
通讯作者：
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DOI：
10.1210/jcem-61-6-1039
发表时间：
1985
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
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影响因子：
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作者：
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DOI：
10.1016/0002-9343(81)90423-x
发表时间：
1981
期刊：
The American journal of medicine
影响因子：
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作者：
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通讯作者：
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影响因子：
15.9
作者：
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通讯作者：
OLEFSKY, JM