Quentmeier A, Daneschmand H, Klein H, Unthan-Fechner K, Probst I
Institut für Biochemie, Fachbereich Medizin, Georg-August-Universität Göttingen, Federal Republic of Germany.
Biochem J. 1993 Jan 15;289 ( Pt 2)(Pt 2):549-55. doi: 10.1042/bj2890549.
The actions of the phorbol ester phorbol 12-myristate 13-acetate (PMA) on glucose metabolism, amino acid transport and enzyme inductions were studied in primary cultures of adult-rat hepatocytes and compared with the effects of insulin. PMA and insulin stimulated glycolysis 5- and 7-fold respectively. The half-maximal effective dose of PMA was 60 nM. Stimulation of glycolysis was accompanied by an insulin- or PMA-dependent and okadaic acid-sensitive activation of 6-phosphofructo-2-kinase and pyruvate kinase, as well as by an increase in fructose 2,6-bisphosphate. Glucose production from glycogen was decreased to 50% by PMA and to 15% by insulin, whereas glycogen synthesis was stimulated 2- and 7-fold respectively. PMA also increased aminoisobutyrate uptake, induced ornithine decarboxylase and counteracted the glucagon-dependent induction of phosphoenolpyruvate carboxykinase. PMA strongly antagonized the hormonal activation of glycogen synthesis, but all other insulin actions assayed were not decreased by the phorbol ester. Whereas additive effects of PMA and insulin were not detected, PMA and a simultaneous increase in the glucose concentration had additive effects on glycolysis and glycogen metabolism. Cell exposure to insulin resulted in receptor autophosphorylation and a more than 10-fold activation of the receptor tyrosine kinase. PMA did not alter these effects, and also had no effect on the receptor phosphorylation status in the absence of insulin. Long-term (15 h) pretreatment of the cells with PMA abolished all PMA effects, but not the insulin effects. It is concluded that PMA does not generally antagonize the action of insulin in differentiated adult hepatocytes, and that insulin and PMA may use related signal-transduction pathways.
研究了佛波酯佛波醇12 -肉豆蔻酸酯13 -乙酸酯（PMA）对成年大鼠肝细胞原代培养物中葡萄糖代谢、氨基酸转运和酶诱导的作用，并与胰岛素的作用进行了比较。PMA和胰岛素分别刺激糖酵解5倍和7倍。PMA的半数有效剂量为60 nM。糖酵解的刺激伴随着6 -磷酸果糖-2 -激酶和丙酮酸激酶的胰岛素或PMA依赖性及冈田酸敏感性激活，以及果糖2,6 -二磷酸的增加。PMA使糖原的葡萄糖生成减少至50%，胰岛素使其减少至15%，而糖原合成分别被刺激2倍和7倍。PMA还增加了氨基异丁酸的摄取，诱导了鸟氨酸脱羧酶，并对抗了胰高血糖素依赖性的磷酸烯醇式丙酮酸羧激酶的诱导。PMA强烈拮抗糖原合成的激素激活，但所检测的所有其他胰岛素作用均未被佛波酯降低。虽然未检测到PMA和胰岛素的相加作用，但PMA和葡萄糖浓度的同时增加对糖酵解和糖原代谢有相加作用。细胞暴露于胰岛素导致受体自身磷酸化以及受体酪氨酸激酶激活超过10倍。PMA未改变这些作用，并且在无胰岛素时对受体磷酸化状态也无影响。用PMA对细胞进行长期（15小时）预处理消除了所有PMA的作用，但未消除胰岛素的作用。结论是，PMA一般不拮抗分化的成年肝细胞中胰岛素的作用，并且胰岛素和PMA可能使用相关的信号转导途径。
