Effect of rhIGF-I infusion on whole fetal and fetal skeletal muscle protein metabolism in sheep

被引:15
作者
Boyle, DW
Denne, SC
Moorehead, H
Lee, WH
Bowsher, RR
Liechty, EA
机构
[1] Indiana Univ, Sch Med, Dept Pediat, Herman B Wells Ctr Pediat Res, Indianapolis, IN 46202 USA
[2] Eli Lilly Res Labs, Indianapolis, IN 46202 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 1998年 / 275卷 / 06期
关键词
phenylalanine; leucine; amino acid kinetics; hindlimb metabolism; glucose uptake; oxygen uptake; recombinant human insulin-like growth factor I;
D O I
10.1152/ajpendo.1998.275.6.E1082
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Insulin-like growth factor I (IGF-I) has been shown to have significant anabolic effects in the regulation of fetal protein metabolism. To investigate the tissue-specific effects of IGF-I on fetal skeletal muscle metabolism, we infused recombinant human (rh) IGF-I directly into the hindlimb of nine chronically catheterized, late-gestation fetal sheep. Substrate balance and amino acid kinetics were measured across the hindlimb and were compared with the effects at the whole body level before and during a 3-h infusion of rhIGF-I into the external iliac artery at 150 mu g/h. Infusion of rhIGF-I resulted in increases in IGF-I concentrations by 2- to 5.75-fold in the ipsilateral iliac vein and by nearly 3-fold in the abdominal aorta. In the study limb, IGF-I had no effect on protein synthesis (phenylalanine rate of disposal 0.88 +/- 0.13 before vs. 0.73 +/- 0.19 mu mol/min during IGF-I) or breakdown (phenylalanine rate of appearance 0.67 +/- 0.13 before vs. 0.60 +/- 0.17 mu mol/min during IGF-I) and did not alter net phenylalanine balance. IGF-I also did not affect hindlimb oxygen or glucose uptake. In contrast, at the whole body level, the rate of appearance of leucine, indicative of fetal protein breakdown, decreased during IGF-I infusion (rate of appearance of leucine 41.1 +/- 3.3 to 37.6 +/- 2.7 mu mol/min) as did fetal leucine oxidation (8.4 +/- 0.8 to 6.8 +/- 0.6 mu mol/min). There was no change in the umbilical uptake of leucine, and although not statistically significant, fetal leucine accretion increased 2.4-fold. These results provide further evidence that IGF-I promotes fetal protein accretion; however, its site of action is in tissues other than skeletal muscle.
引用
收藏
页码:E1082 / E1091
页数:10
相关论文
共 50 条
[1]   INSULIN-LIKE GROWTH-FACTORS (IGF)-1 AND (IGF)-2 IN HUMAN-FETAL PLASMA AND RELATIONSHIP TO GESTATIONAL-AGE AND FETAL SIZE DURING MIDPREGNANCY [J].
ASHTON, IK ;
ZAPF, J ;
EINSCHENK, I ;
MACKENZIE, IZ .
ACTA ENDOCRINOLOGICA, 1985, 110 (04) :558-563
[2]   AN ISOTOPIC METHOD FOR MEASUREMENT OF MUSCLE PROTEIN-SYNTHESIS AND DEGRADATION INVIVO [J].
BARRETT, EJ ;
REVKIN, JH ;
YOUNG, LH ;
ZARET, BL ;
JACOB, R ;
GELFAND, RA .
BIOCHEMICAL JOURNAL, 1987, 245 (01) :223-228
[3]   CHANGES IN IGF-I AND IGF-II EXPRESSION AND SECRETION DURING THE PROLIFERATION AND DIFFERENTIATION OF NORMAL RAT OSTEOBLASTS [J].
BIRNBAUM, RS ;
BOWSHER, RR ;
WIREN, KM .
JOURNAL OF ENDOCRINOLOGY, 1995, 144 (02) :251-259
[4]   IGF-I AND INSULIN-RECEPTORS IN BOVINE SKELETAL-MUSCLE - COMPARISONS OF DIFFERENT DEVELOPMENTAL AGES, 2 DIFFERENT GENOTYPES AND VARIOUS INDIVIDUAL MUSCLES [J].
BOGE, A ;
SAUERWEIN, H ;
MEYER, HHD .
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES, 1995, 103 (02) :99-104
[5]  
Bonds D R, 1980, J Dev Physiol, V2, P409
[6]   MEASUREMENT OF INSULIN-LIKE GROWTH FACTOR-II IN PHYSIOLOGICAL FLUIDS AND TISSUES .1. AN IMPROVED EXTRACTION PROCEDURE AND RADIOIMMUNOASSAY FOR HUMAN AND RAT-FLUIDS [J].
BOWSHER, RR ;
LEE, WH ;
APATHY, JM ;
OBRIEN, PJ ;
FERGUSON, AL ;
HENRY, DP .
ENDOCRINOLOGY, 1991, 128 (02) :805-814
[7]   Effect of prolonged uterine blood flow reduction on fetal growth in sheep [J].
Boyle, DW ;
Lecklitner, S ;
Liechty, EA .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 1996, 270 (01) :R246-R253
[8]   EFFECT OF MATERNAL FASTING ON FETAL GROWTH, SERUM INSULIN-LIKE GROWTH-FACTORS (IGFS), AND TISSUE IGF MESSENGER RIBONUCLEIC-ACIDS [J].
DAVENPORT, ML ;
DERCOLE, AJ ;
UNDERWOOD, LE .
ENDOCRINOLOGY, 1990, 126 (04) :2062-2067
[9]   TISSUE AND PLASMA SOMATOMEDIN-C/INSULIN-LIKE GROWTH FACTOR-I CONCENTRATIONS IN THE HUMAN-FETUS DURING THE 1ST-HALF OF GESTATION [J].
DERCOLE, AJ ;
HILL, DJ ;
STRAIN, AJ ;
UNDERWOOD, LE .
PEDIATRIC RESEARCH, 1986, 20 (03) :253-255
[10]   THE EFFECTS OF INFUSION OF INSULIN-LIKE GROWTH-FACTOR (IGF)-I, IGF-II, AND INSULIN ON GLUCOSE AND PROTEIN-METABOLISM IN FASTED LAMBS [J].
DOUGLAS, RG ;
GLUCKMAN, PD ;
BALL, K ;
BREIER, B ;
SHAW, JHF .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 88 (02) :614-622