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Leptin secretion and protein kinase A activity

机译:瘦素分泌和蛋白激酶A活性

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Leptin is an adipocyte-derived hormone participating in the regulation of food intake and energy balance. Its secretion from fat cells is potentiated by insulin and by substrates providing ATP, whereas factors increasing cAMP level attenuate hormone release stimulated by insulin and glucose. The present experiments were aimed to determine the effect of cAMP on leptin secretion stimulated by glucose, alanine or leucine in the presence of insulin. Moreover, the effect of protein kinase A inhibition on leptin secretion was tested. To stimulate leptin secretion, isolated rat adipocytes were incubated for 2 h in the buffer containing 5 mmol/l glucose, 10 mmol/l alanine or 10 mmol/l leucine, all in the presence of 10 nmol/l insulin. Inhibition of protein kinase A (PKA) by H-89 (50 mu mol/l) slightly enhanced leptin release stimulated by glucose and leucine but not by alanine. Activation of this enzyme by dibutyryl-cAMP (I mmol/l) substantially restricted leptin secretion stimulated by glucose, alanine and leucine. The inhibitory influence of dibutyrylcAMP on leptin secretion was totally (in the case of stimulation induced by glucose) or partially (in the case of stimulation by alanine and leucine) suppressed by H-89. These results demonstrate that leptin secretion induced by glucose, alanine and leucine is profoundly attenuated by cAMP in PKA-dependent manner. Therefore, the action of different stimulators of leptin secretion may be restricted by agents increasing the cAMP content in adipocytes. Moreover, it has also been shown that inhibition of PKA evokes the opposite effect and enhances leptin release.
机译:瘦素是脂肪细胞来源的激素,参与食物摄入和能量平衡的调节。它从脂肪细胞的分泌被胰岛素和提供ATP的底物增强,而增加cAMP水平的因子减弱了胰岛素和葡萄糖刺激的激素释放。本实验旨在确定cAMP对在胰岛素存在下葡萄糖,丙氨酸或亮氨酸刺激的瘦素分泌的影响。此外,测试了蛋白激酶A抑制对瘦蛋白分泌的影响。为了刺激瘦素分泌,将分离的大鼠脂肪细胞在含有5 mmol / l葡萄糖,10 mmol / l丙氨酸或10 mmol / l亮氨酸的缓冲液中孵育10小时,所有时间均为10 nmol / l胰岛素。 H-89(50μmol/ l)对蛋白激酶A(PKA)的抑制作用会稍微增强葡萄糖和亮氨酸刺激的瘦素释放,但丙氨酸不能。通过二丁酰-cAMP(1 mmol / l)激活该酶,基本上限制了葡萄糖,丙氨酸和亮氨酸刺激的瘦素分泌。 H-89完全抑制了丁二酸AMP对瘦素分泌的抑制作用(在葡萄糖诱导的情况下)或部分抑制(在丙氨酸和亮氨酸刺激的情况下)。这些结果表明,cAMP以依赖PKA的方式大大减弱了葡萄糖,丙氨酸和亮氨酸诱导的瘦蛋白分泌。因此,瘦素分泌的不同刺激物的作用可能被增加脂肪细胞中cAMP含量的药物所限制。此外,还显示出对PKA的抑制引起相反的作用并增强瘦素释放。

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