Katz L E, Satin-Smith M S, Collett-Solberg P, Baker L, Stanley C A, Cohen P
Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, 19104, USA.
J Clin Endocrinol Metab. 1998 Dec;83(12):4426-30. doi: 10.1210/jcem.83.12.5347.
Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) gene transcription is known to be inhibited by insulin in vivo and in vitro. Levels of IGFBP-1 typically rise during fasting but also rise after acute hypoglycemia, including that induced by insulin, through an unknown mechanism that may involve counterregulatory hormones such as cortisol. To study the regulation of IGFBP-1 secretion during fasting, we measured IGFBP-1, insulin, cortisol, GH, and glucose during the course of standardized fasting studies in a total of 21 children. The fasting studies lasted 13-32 h and were terminated for a whole-blood glucose concentration of less than 50 mg/dL (2.8 mmol). Of the children studied, 9 children had no disorder, 8 had ketotic hypoglycemia, 2 had isolated GH deficiency, and 2 had fatty acid oxidation disorders. During fasting, IGFBP-1 rose above the mean baseline levels of 28+/-5 ng/mL to a mean level+/-SEM of 336+/-59 ng/mL at the time of hypoglycemia (P=0.001). IGFBP-1 was strongly associated with serum insulin and cortisol levels over the entire course of fasting (P < 0.0001)). The interaction of the 2 hormones across time was also strongly significant (P < 0.0001). There was no statistically significant association between IGFBP-1 and GH or glucose. At the time of hypoglycemia, insulin levels were suppressed to 1.7 microU/mL or less, and there was no correlation between IGFBP-1 levels at the end of fasting and final insulin level. In contrast, cortisol levels correlated with IGFBP-1 in the final hypoglycemic sample (r=0.56, P < 0.01). Partial correlation analysis revealed that the relationship between IGFBP-1 and cortisol was unchanged when the data was controlled for insulin levels. These data show that insulin and cortisol both regulate IGFBP-1 secretion during fasting; the effects of insulin and cortisol are strong during the course of fasting. Significant hypoglycemia stimulates a further rise in IGFBP-1, which seems to be regulated, in part, by cortisol. The cortisol-induced rise in IGFBP-1 during fasting and during hypoglycemia potentially serves to prevent the hypoglycemic effects of free IGFs.
胰岛素样生长因子（IGF）结合蛋白-1（IGFBP-1）基因转录在体内和体外均已知受胰岛素抑制。IGFBP-1水平在禁食期间通常会升高，但在急性低血糖（包括胰岛素诱导的低血糖）后也会升高，其机制不明，可能涉及诸如皮质醇等反调节激素。为研究禁食期间IGFBP-1分泌的调节，我们在总共21名儿童的标准化禁食研究过程中测量了IGFBP-1、胰岛素、皮质醇、生长激素（GH）和葡萄糖。禁食研究持续13 - 32小时，当全血葡萄糖浓度低于50mg/dL（2.8mmol）时终止。在所研究的儿童中，9名儿童无疾病，8名患有酮症性低血糖，2名患有孤立性生长激素缺乏症，2名患有脂肪酸氧化障碍。禁食期间，IGFBP-1在低血糖时从平均基线水平28±5ng/mL升高至平均水平±标准误336±59ng/mL（P = 0.001）。在禁食的整个过程中，IGFBP-1与血清胰岛素和皮质醇水平密切相关（P < 0.0001）。这两种激素随时间的相互作用也非常显著（P < 0.0001）。IGFBP-1与GH或葡萄糖之间无统计学显著关联。在低血糖时，胰岛素水平被抑制至1.7微单位/毫升或更低，禁食结束时的IGFBP-1水平与最终胰岛素水平之间无相关性。相比之下，在最终低血糖样本中，皮质醇水平与IGFBP-1相关（r = 0.56，P < 0.01）。偏相关分析显示，当数据校正胰岛素水平后，IGFBP-1与皮质醇之间的关系不变。这些数据表明，胰岛素和皮质醇在禁食期间均调节IGFBP-1分泌；在禁食过程中，胰岛素和皮质醇的作用很强。显著低血糖会刺激IGFBP-1进一步升高，这似乎部分受皮质醇调节。禁食期间和低血糖期间皮质醇诱导的IGFBP-1升高可能有助于防止游离IGF的低血糖作用。
