Teale J D, Blum W F, Marks V
Department of Clinical Biochemistry, St Luke's Hospital, Guildford, Surrey, UK.
Ann Clin Biochem. 1992 May;29 ( Pt 3):314-23. doi: 10.1177/000456329202900312.
The hypoglycaemia caused by non-islet cell tumours is often associated with an increase in plasma insulin-like activity. In many cases there is a relative if not always absolute increase in plasma insulin-like growth factor II (IGF-II). Growth hormone (GH) secretion is almost invariably depressed as is the plasma insulin response to oral glucose. Despite the high concentration of IGFs (i.e. IGF-I and IGF-II) normally found in the plasma of healthy people their potential hypoglycaemic effect is not manifest due to the tightness with which they are bound to specific binding proteins (IGFBPs). Plasma levels of the major binding protein (IGFBP-3), which is GH-dependent, were depressed in three patients with tumour induced hypoglycaemia. Treatment with biosynthetic GH restored IGFBP-3 to levels which were approximately equimolar to total plasma IGF concentrations, alleviated the hypoglycaemia and restored the plasma insulin responses to oral glucose. We suggest that after GH treatment IGF-II is sequestered by stimulated IGFBP-3 in association with a pre-existing acid-labile subunit to form high molecular weight complexes which prevent IGF-II gaining access to tissues receptors through which it exerts its hypoglycaemic effects.
非胰岛细胞瘤所致低血糖常伴有血浆胰岛素样活性增加。在许多情况下，血浆胰岛素样生长因子II（IGF-II）即使并非总是绝对增加，也会有相对增加。生长激素（GH）分泌几乎总是受到抑制，对口服葡萄糖的血浆胰岛素反应也是如此。尽管在健康人的血浆中通常可发现高浓度的IGF（即IGF-I和IGF-II），但由于它们与特定结合蛋白（IGFBPs）紧密结合，其潜在的低血糖作用并未显现。在三名肿瘤诱导的低血糖患者中，依赖GH的主要结合蛋白（IGFBP-3）的血浆水平降低。用生物合成GH治疗可使IGFBP-3恢复到与总血浆IGF浓度大致等摩尔的水平，缓解低血糖并恢复对口服葡萄糖的血浆胰岛素反应。我们认为，GH治疗后，IGF-II与预先存在的酸不稳定亚基结合，被刺激产生的IGFBP-3隔离，形成高分子量复合物，阻止IGF-II进入其发挥低血糖作用的组织受体。
