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 Ca2+ and cAMP levels. Depletion of intracellular Ca2+ 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 75kDa 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 Ca2+ and cAMP levels, but is likely linked to the hexosamine biosynthetic pathway.
Endothelin-stimulated glucose uptake: effects of intracellular Ca2+, cAMP and glucosamine
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Jinshyun R. WU-WONG, Cathleen E. BERG, Brian D. DAYTON; Endothelin-stimulated glucose uptake: effects of intracellular Ca2+, cAMP and glucosamine. Clin Sci (Lond) 1 September 2002; 103 (s2002): 418S–423S. doi: https://doi.org/10.1042/CS103S418S
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