Endothelin-stimulated glucose uptake: effects of intracellular Ca(2+), cAMP and glucosamine.
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.
Wu-Wong
Jinshyun R
JR
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL, U.S.A. ruth.r.wuwong@abbott.com
Berg
Cathleen E
CE
Dayton
Brian D
BD
D016475:3T3 Cells; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D020536:Enzyme Activators / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005944:Glucosamine / Q000378:metabolism* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006595:Hexosamines / Q000096:biosynthesis; D007328:Insulin / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D012795:Sialoglycoproteins / Q000378:metabolism; D013268:Stimulation, Chemical
D019332:Endothelin-1; D020536:Enzyme Activators; D006595:Hexosamines; C507764:Il1rn protein, mouse; D007328:Insulin; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D005947:Glucose; D007545:Isoproterenol; D005944:Glucosamine; D002118:Calcium