Szkudelski T, Nowicka E, Szkudelska K
Department of Animal Physiology and Biochemistry, August Cieszkowski University of Agriculture, 60-637 Wołyńska 35, Poznań, Poland.
Physiol Res. 2005;54(1):79-85. doi: 10.33549/physiolres.930570.
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 micromol/l) slightly enhanced leptin release stimulated by glucose and leucine but not by alanine. Activation of this enzyme by dibutyryl-cAMP (1 mmol/l) substantially restricted leptin secretion stimulated by glucose, alanine and leucine. The inhibitory influence of dibutyryl-cAMP 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.
瘦素是一种由脂肪细胞分泌的激素，参与食物摄入和能量平衡的调节。胰岛素和提供ATP的底物可增强其从脂肪细胞中的分泌，而提高cAMP水平的因子则会减弱胰岛素和葡萄糖刺激的激素释放。本实验旨在确定在存在胰岛素的情况下，cAMP对葡萄糖、丙氨酸或亮氨酸刺激的瘦素分泌的影响。此外，还测试了蛋白激酶A抑制对瘦素分泌的作用。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2小时，所有这些均在10 nmol/l胰岛素存在的情况下进行。用H-89（50 μmol/l）抑制蛋白激酶A（PKA）可略微增强葡萄糖和亮氨酸刺激的瘦素释放，但对丙氨酸刺激的瘦素释放无增强作用。用二丁酰-cAMP（1 mmol/l）激活该酶可显著限制葡萄糖、丙氨酸和亮氨酸刺激的瘦素分泌。H-89完全（在葡萄糖诱导的刺激情况下）或部分（在丙氨酸和亮氨酸刺激的情况下）抑制了二丁酰-cAMP对瘦素分泌的抑制作用。这些结果表明，葡萄糖、丙氨酸和亮氨酸诱导的瘦素分泌以PKA依赖的方式被cAMP显著减弱。因此，增加脂肪细胞中cAMP含量的试剂可能会限制瘦素分泌不同刺激物的作用。此外，还表明抑制PKA会产生相反的效果并增强瘦素释放。
