Study for pathophysiological significance insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs)

胰岛素样生长因子（IGFs）与特异性结合蛋白（IGFBPs）结合，并推测IGFBPs可能调节IGF的作用。在这项研究中，我们研究了IGFs和IGFBPs的病理生理意义如下。1)神经性厌食症中的IGFs和IGFBPs：营养不良导致血清IGF-I水平降低，与IGFBPs谱改变相关。为了进一步阐明营养状况对血清IGFs和IGFBPs水平的影响，我们对48例神经性厌食症患者进行了调查。用免疫放射分析法测定66例患者血清中IGF-1、IGF-2、IGFBP-3水平。血清IGF-I和IGFBP-3水平低于正常人，其值与作为营养参数的BMI呈正相关（分别为r=0.54 ; p<0.001和r=0.42 ; p<0.001）。血清IGFBP-2水平与BMI呈负相关（r=0. 999，P < 0. 05）。 ...更多信息 60 ; p<0.001）。此外，我们还发现，这些患者血清IGFBP-2水平的升高与BMI的改善一致。血清IGF-II水平与BMI无相关性（r=0.23 ; p=0.06）。为了进一步研究与BMI的相关性，计算了偏相关系数，血清IGFBP-2的值高于IGF-I、IGFBP-3和IGF-II的值。这些数据表明，血清IGFBP-2、IGF-I和IGFBP-3水平是神经性厌食症患者的营养预测因子，并且血清IGFBP-2比IGF-I和IGFBP-3更好地预测。2）IGF和IGFBP在产生IGF-II的非胰岛细胞肿瘤低血糖症（NICTH）中：在产生NICTH的IGF-II患者中，血清IGF-II水平范围为294 - 1492 ng/ml，平均为718 ± 0.5ng/ml。[)53 IGF-II水平仅在13例患者中升高（正常范围：378-804 ng/ml）。所有患者的血清IGF-I水平均较低，平均为22.7 ± 0.01。[)2.2 ng/ml（正常范围：88-240 ng/ml）。IRMA法测得的血清IGFBP-3水平显著低于正常人（1.51 ± 0.01）。[）0.11 vs.3.13（]SY. ±. 0.05 μ g/ml ; p<0.001）。血清IGFBP-2水平显著高于正常人（1982年）。[)208与383（]SY. ±. [)20 ng/ml：p<0.001）。成功切除肿瘤后，血清IGFBP-2水平下降，IGFBP-3水平正常化。血清IGFBPs水平的改变可能与产生NICTH的IGF-II中的生物可利用IGF-II有关。3）NICTH中IGF-II基因的印记丢失（LOI）：IGF-II基因（IGF 2）是母系印记的。最近，在一些胚胎性肿瘤中已经报道了IGF 2的LOI，这表明该基因的双等位基因表达导致IGF-II肽的过表达和促有丝分裂活性的增加。在这项研究中，我们检查了NICTH肿瘤中IGF 2的LOI。11个信息性肿瘤中有8个呈双等位基因表达（LOI），这表明IGF 2的LOI可能与NICTH肿瘤中的IGF 2的LOI无关。

Insulin-like growth factors (IGFs) bind to specific binding proteins (IGFBPs), and it has been speculated that the IGFBPs might modulate IGF action. In this study, we have investigated pathophysiological significance of IGFs and IGFBPs as follows. 1)IGFs and IGFBPs in anorexia nervosa : Malnutrition results in decreased serum IGF-I levels associated with altered profiles of IGFBPs. In the present study, to clarify further the effect of the nutritional status on the serum IGFs and IGFBPs levels, we investigated 48 patients with aunorexia nervosa. lGF-I,-II and lGFBP-3 levels by lRMA and IGFBP-2 levels by RIA were measured in 66 serum samples from the patients. The serum IGF-I and IGFBP-3 levels were lower than those in normal subjects, and the values positively correlated with the BMI as a nutritional parameter (r=0.54 ; p<0.001, and r=0.42 ; p<0.001, respectively). The serum IGFBP-2 levels were remarkably elevated in these patients and the levels inversely correlated with the BMI (r=0. … More 60 ; p<0.001). Funthemore, we found that the elevated serum IGFBP-2 levels decreased in accordance with the improvement of the BMI in these patients. The serum IGF-II levels did not correlate with the BMI (r=0.23 ; p=0.06). To investigate the correlation with the BMI further, the partial correlation coefficients were calculated, and the value for serum IGFBP-2 was higher than those for IGF-I,IGFBP-3, and IGF-II.These data indicate that serum IGFBP-2, IGF-I and IGFBP-3 levels are nutritional predictors in the patients with anorexia nervosa, and serum IGFBP-2 is better predictor than the IGF-I and IGFBP-3.2)IGFs and IGFBPs in IGF-II producing non-islet cell tumor hypoglycemia (NICTH) : In the patients with IGF-II producing NICTH, serum lGF-II levels ranged from 294 to l492 ng/ml with a mean of 718(]SY.+-。[)53 ng/ml, and the elevated IGF-II levels were found in only 13 patients (Normal range : 378-804 ng/ml). Serum IGF-I levels were low in all patients, with a mean of 22.7(]SY.+-。[)2.2 ng/ml (Normal range : 88-240 ng/ml). The serum IGFBP-3 levels by IRMA were significantly lower than those in normal subjects (1.51 (]SY.+-。[) 0.11 vs.3.13(]SY.+-。[)0.05 mug/ml ; p<0.001). The serum IGFBP-2 levels by RIA were significantly greater than those in normal subjects (1982(]SY.+-。[)208 vs.383(]SY.+-。[)20 ng/ml : p<0.00l). After successful tumor resection, serum IGFBP-2 levels decreased and the IGFBP-3 levels were normalized. The altered levels of serum IGFBPs could be related to bioavailable IGF-II in the IGF-II producing NICTH.3)Loss of imprinting (LOI) of IGF-II gene in NICTH : IGF-II gene (IGF2) is maternally imprinted. Rrcently, LOI of IGF2 has been reported in some embryonal tumors, suggesting that biallelic expression of the gene leads to overexpression of IGF-II peptide and increased mitogenic activity. In this study, we examined LOI of IGF2 in tumor from NICTH.IGF2 was expressed biallelically (LOI) in 8 of 11 informative tumors, suggesting that LOI of IGF2 could be relat Less