Wu-Wong Jinshyun R, Berg Cathleen E, Dayton Brian D
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL, U.S.A.
Clin Sci (Lond). 2002 Aug;103 Suppl 48:418S-423S. doi: 10.1042/CS103S418S.
Endothelin-1 (ET-1) is a 21-amino-acid peptide that binds to G-protein-coupled receptors to evoke biological responses. Previously we have shown that ET-1 stimulates glucose uptake in 3T3-L1 adipocytes and neonatal rat cardiomyocytes, but the mechanism is not completely understood. ET-1 is known to modulate intracellular Ca(2+) and cAMP levels. Depletion of intracellular Ca(2+) by treating 3T3-L1 adipocytes with EDTA and 1,2-bis(2-amino-5-methylphenoxy)ethane-N,N,N',N'-tetra-acetic acid tetra-acetoxymethyl ester (MAPTAM) did not have a significant effect on ET-1-induced glucose uptake. Forskolin, a potent stimulator which stimulates adenylate cyclase and increases the intracellular cAMP level, partially inhibited insulin-stimulated glucose uptake in 3T3-L1 cells, but had no significant impact on the effect of ET-1. Forskolin also did not show an effect on the tyrosine phosphorylation of a 75 kDa protein induced by ET-1. Glucosamine treatment causes insulin resistance in cells, possibly by entering the hexosamine biosynthetic pathway. In neonatal rat cardiomyocytes, glucosamine treatment blocked both insulin and ET-1-stimulated glucose uptake and also eliminated the translocation of IRAP, an aminopeptidase in GLUT4-containing vesicles, from the cytoplasm to the plasma membrane. These results suggest that ET-1-induced glucose uptake is independent of its effects on modulating intracellular Ca(2+) and cAMP levels, but is likely linked to the hexosamine biosynthetic pathway.
内皮素 -1（ET -1）是一种由21个氨基酸组成的肽，它与G蛋白偶联受体结合以引发生物学反应。此前我们已经表明，ET -1可刺激3T3 -L1脂肪细胞和新生大鼠心肌细胞摄取葡萄糖，但其机制尚未完全明确。已知ET -1可调节细胞内Ca(2+)和cAMP水平。用EDTA和1,2 -双（2 -氨基 -5 -甲基苯氧基）乙烷 -N,N,N',N' -四乙酸四乙酰氧甲酯（MAPTAM）处理3T3 -L1脂肪细胞以耗尽细胞内Ca(2+)，对ET -1诱导的葡萄糖摄取没有显著影响。福斯高林是一种有效的刺激剂，可刺激腺苷酸环化酶并提高细胞内cAMP水平，它部分抑制了3T3 -L1细胞中胰岛素刺激的葡萄糖摄取，但对ET -1的作用没有显著影响。福斯高林对ET -1诱导的75 kDa蛋白的酪氨酸磷酸化也没有作用。氨基葡萄糖处理可导致细胞产生胰岛素抵抗，可能是通过进入己糖胺生物合成途径。在新生大鼠心肌细胞中，氨基葡萄糖处理阻断了胰岛素和ET -1刺激的葡萄糖摄取，并且还消除了含GLUT4囊泡中的氨肽酶IRAP从细胞质向质膜的转运。这些结果表明，ET -1诱导的葡萄糖摄取与其对调节细胞内Ca(2+)和cAMP水平的作用无关，但可能与己糖胺生物合成途径有关。
