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

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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