Production of insulin-like growth factor I and its binding protein in rat hepatocytes cultured from diabetic and insulin-treated diabetic rats.
Production of insulin-like growth factor I and its binding protein in rat hepatocytes cultured from diabetic and insulin-treated diabetic rats.
复制标题
糖尿病大鼠和经胰岛素治疗的糖尿病大鼠培养的大鼠肝细胞中胰岛素样生长因子 I 及其结合蛋白的产生。
作者：
C. Scott;R. Baxter
本研究探讨了实验性糖尿病对大鼠胰岛素样生长因子I（rIGF-I）及其结合蛋白（IGF-BP）释放的成年大鼠肝细胞在原代培养的影响。与年龄匹配的未治疗大鼠（1 U = 770 ng人IGF-I）的1.06 +/-0.04相比，链脲佐菌素（75 mg/kg）治疗大鼠的血清rIGF-I值降低了0.37 +/-0.04 U/ml。从糖尿病大鼠分离的肝细胞中也观察到rIGF-I（正常大鼠细胞中的15%）和IGF-BP（正常的30%）的肝细胞生成率同时降低。胰岛素替代治疗（1.2 U/天）3-4天使血清rIGF-I水平正常化（0.92 +/- 0.07 U/ml），分离的肝细胞产生的rIGF-I增加到正常细胞的67%，IGF-BP产生增加到正常的70%。链脲佐菌素处理的大鼠在体内用rGH（150微克/天）处理7天未能增加血清rIGF-I水平或肝细胞产生rIGF-I。体外胰岛素（3 × 10（-7）M）可增加非糖尿病大鼠肝细胞释放rIGF-I，但对糖尿病动物细胞无影响，表明在糖尿病中维持rIGF-I合成需要胰岛素以外的因素。在本研究中使用的动物中，血清rIGF-I水平与肝细胞rIGF-I产生具有很强的相关性。然而，基于这些值计算循环rIGF-I半衰期显示，糖尿病大鼠（7.91 +/- 1.58 h）和rGH治疗糖尿病大鼠（7.52 +/- 1.25 h）的半衰期是非糖尿病动物（2.99 +/- 0.35 h）和胰岛素治疗糖尿病动物（3.85 +/- 0.36 h）的2倍。这表明糖尿病动物中循环rIGF-I的清除率可能较慢。
This study examines the effect of experimental diabetes on the release of rat insulin-like growth factor I (rIGF-I) and its binding protein (IGF-BP) by adult rat hepatocytes in primary culture. Rats treated with streptozotocin (75 mg/kg) had decreased serum rIGF-I values of 0.37 +/- 0.04 U/ml compared to 1.06 +/- 0.04 in age-matched untreated rats (1 U = 770 ng human IGF-I). Concomitant decreases in hepatocyte production rates for rIGF-I (15% of the rate in cells from normal rats) and IGF-BP (30% of normal) were also observed for hepatocytes isolated from diabetic rats. Insulin replacement therapy (1.2 U/day) for 3-4 days normalized serum rIGF-I levels (0.92 +/- 0.07 U/ml) and increased rIGF-I production by isolated hepatocytes to 67% the rate of normal cells and IGF-BP production to 70% normal. Treatment of streptozotocin-treated rats with rGH (150 micrograms/day) in vivo for 7 days failed to increase serum rIGF-I levels or hepatocyte production of rIGF-I. Insulin in vitro (3 X 10(-7) M) increased rIGF-I release by hepatocytes from nondiabetic rats, but had no effect on cells from diabetic animals, suggesting that factors other than insulin are required to maintain rIGF-I synthesis in diabetes. Serum rIGF-I levels showed a strong correlation with hepatocyte rIGF-I production in the animals used in this study. However, calculation of circulating rIGF-I half-life based on these values showed a 2-fold higher half-life in diabetic rats (7.91 +/- 1.58 h) and rGH-treated diabetic rats (7.52 +/- 1.25 h) than in nondiabetic (2.99 +/- 0.35 h) and insulin-treated diabetic animals (3.85 +/- 0.36 h). This suggests that the rate of clearance of circulating rIGF-I may be slower in diabetic animals.
DOI：
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发表时间：
1986-01
期刊：
The Journal of biological chemistry
影响因子：
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作者：
T. B. Miller;A. Garnache;J. Cruz;R. McPherson;C. Wolleben
通讯作者：
T. B. Miller;A. Garnache;J. Cruz;R. McPherson;C. Wolleben
DOI：
10.1073/pnas.81.3.935
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
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作者：
DERCOLE, AJ;STILES, AD;UNDERWOOD, LE
通讯作者：
UNDERWOOD, LE