FLUCTUATIONS IN AFFINITY AND CONCENTRATION OF INSULIN RECEPTORS ON CIRCULATING MONOCYTES OF OBESE PATIENTS - EFFECTS OF STARVATION, REFEEDING, AND DIETING

FLUCTUATIONS IN AFFINITY AND CONCENTRATION OF INSULIN RECEPTORS ON CIRCULATING MONOCYTES OF OBESE PATIENTS - EFFECTS OF STARVATION, REFEEDING, AND DIETING
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DOI:
10.1172/jci108565
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发表时间:
1976-01-01
影响因子:
15.9
通讯作者:
DEMEYTS, P
DEMEYTS, P
中科院分区:
医学1区
文献类型:
--
作者:
BAR, RS;GORDEN, P;DEMEYTS, P

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在不同饮食状态下测定了肥胖患者和正常志愿者循环单核细胞上 125I-胰岛素与胰岛素受体的结合。在基础、进食状态下,患有临床胰岛素抵抗的肥胖患者 (n = 6) 的单核细胞结合的胰岛素少于正常人 (n = 10),因为胰岛素受体浓度降低(肥胖 = 6000-13,000 个位点/单核细胞,正常人为 15,000-28,000 个位点/单核细胞)。没有临床胰岛素抵抗证据的单一肥胖患者表现出胰岛素与每个单核细胞 16,000 个位点的正常结合。在所有患者中,总受体浓度与禁食过夜后静息时测量的胰岛素循环水平呈负相关。对于胰岛素结合基础降低的肥胖患者,48-72小时内循环胰岛素快速降低,结合增加至正常水平,但仅在低激素浓度下; 125I-胰岛素结合的这种有限的正常化与受体对胰岛素的亲和力增加有关,而受体浓度却没有变化。急性禁食期后重新进食导致恢复到在基础进食状态下观察到的升高的血浆胰岛素水平、基础受体亲和力和降低的胰岛素结合。长期饮食使血浆胰岛素水平、胰岛素结合和受体浓度恢复正常,而亲和力没有变化。人类单核细胞的胰岛素受体可能比肥胖小鼠和培养的人类淋巴细胞的受体对环境胰岛素的调节更敏感。通过改变受体浓度和改变现有受体的亲和力,胰岛素受体在体内对其与胰岛素的相互作用进行调节。
The binding of 125I-insulin to insulin receptors on circulating monocytes of obese patients and normal volunteers was determined under various dietary states. In the basal, fed state the monocytes of obese patients with clinical insulin resistance (n = 6) bound less insulin than normals (n = 10) because of a decrease in insulin receptor concentration (obese = 6000-13,000 sites/monocyte vs. normals 15,000-28,000 sites/monocyte). The single obese patient without evidence of clinical insulin resistance demonstrated normal binding of insulin with 16,000 sites/monocyte. In all patients the total receptor concentration was inversely related to the circulating levels of insulin measured at rest after an overnight fast. For the obese patients with basally depressed insulin binding, a 48-72 h fast lowered circulating insulin and increased binding to normal levels but only at low hormone concentrations; this limited normalization of 125I-insulin binding was associated with increased receptor affinity for insulin without change in receptor concentration. Refeeding after the acute fasting periods resulted in return to the elevated plasma insulin levels, the basal receptor affinity and the depressed insulin binding observed in the basal, fed state. Chronic diet restored plasma insulin levels, insulin binding, and receptor concentration to normal without change in affinity. The insulin receptor of human monocytes is probably more sensitive to regulation by ambient insulin than the receptors of obese mice and cultured human lymphocytes. An insulin receptor undergoes in vivo modulation of its interaction with insulin by changing receptor concentration and by altering the affinity of existing receptors.