Effects of chronic renal failure on plasma clearance of insulin-like growth factor I, des-(1-3)IGF-I, and LR(3)IGF-I

被引:6
作者
Gillespie, CM
Hazel, SJ
Walton, PE
Martin, AA
机构
[1] CHILD HLTH RES INST, COOPERAT RES CTR TISSUE GROWTH & REPAIR, ADELAIDE, SA 5006, AUSTRALIA
[2] CSIRO, DIV HUMAN NUTR, ADELAIDE, SA 5000, AUSTRALIA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 1996年 / 271卷 / 04期
关键词
insulin-like growth factor I analogues; insulin-like growth factor I-binding proteins; insulin-like growth factor pharmacokinetics; organ distribution of insulin-like growth factors;
D O I
10.1152/ajpendo.1996.271.4.E649
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Using a rat model of chronic renal failure (CRF), we examined insulin-like growth factor I(IGF-I) clearance, degradation, organ distribution, and IGF binding profiles in plasma. The effects of IGF-binding proteins (IGFBP) on IGF clearance and degradation in CRF were studied using the IGF-I analogues des-(1-3)IGF-I and LR(3)IGF-I, which bind poorly to IGFBP. Although total clearance of IGF-I was not significantly altered in CRF, half-life and area under the curve were increased in the rapid distribution phase and were reduced in the slow elimination phase. Total clearance of LR(3)IGF-I was significantly increased. Reduced binding of IGF-I in the 150-kDa complex and increased binding to smaller-molecular-weight IGFBP were observed in CRF. Increased degradation of both IGF-I and LR(3)IGF-I was associated with reduced IGF binding in the 150-kDa complex. The results suggest that the accumulation of lower-molecular-weight IGFBP with reduced IGF binding in the 150-kDa complex, associated with increased degradation of peptide, may explain, at least in part, the reduced bioactivity of IGF-I observed in CRF.
引用
收藏
页码:E649 / E657
页数:9
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