METABOLIC ACTIONS OF INSULIN-LIKE GROWTH FACTOR-I IN CULTURED-HEPATOCYTES FROM ADULT-RATS

被引:32
作者
HARTMANN, H [1 ]
SCHMITZ, F [1 ]
CHRIST, B [1 ]
JUNGERMANN, K [1 ]
CREUTZFELDT, W [1 ]
机构
[1] UNIV GOTTINGEN,DEPT BIOCHEM,W-3400 GOTTINGEN,GERMANY
关键词
D O I
10.1002/hep.1840120511
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Short‐term and long‐term regulation of hepatic carbohydrate metabolism by insulinlike growth factor‐I was studied in primary cultures of adult rat hepatocytes and compared with the metabolic potency of insulin. Insulinlike growth factor‐I stimulated the formation of [14C]lactate from [14C]glucose up to three‐fold with a half‐maximally effective concentration of ∼50 nmol/L. Basal glycogenolysis was inhibited by about 20%, and glucagon‐activated glycogenolysis was blocked completely by insulinlike growth factor‐I with half‐maximally effective concentrations of about 1.5 to 2 nmol/L. The activity of the key glycolytic enzymes glucokinase and pyruvate kinase were induced twofold. The glucagon‐dependent induction of phosphoenolpyruvate carboxykinase—the key gluconeogenic enzyme—was antagonized with a half‐maximally effective concentration of about 5 nmol/L. This inhibition of the glucagon‐dependent induction of the enzyme was accompanied by a similar reduction of the increase in phosphoenolpyruvate carboxykinase—mRNA level as assessed by Northern blot analysis. The potency of insulinlike growth factor‐I at half‐maximally effective concentrations was approximately 2% to 4% that of insulin. Because binding studies demonstrated a comparably low affinity of insulinlike growth factor‐I to the insulin receptor, it is suggested that in adult liver—in contrast to fetal and regenerating liver—insulinlike growth factor‐I could exert short‐term and long‐term metabolic effects on parenchymal cells only through interaction with the insulin receptor. (HEPATOLOGY 1990;12:1139–1143). Copyright © 1990 American Association for the Study of Liver Diseases
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页码:1139 / 1143
页数:5
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