Endothelin stimulates glucose uptake via activation of endothelin-A receptor in neonatal rat cardiomyocytes.
Endothelin-1 (ET-1) is a 21 amino acid peptide that binds to G-protein-coupled receptors to evoke biological responses. Previously we have found that ET-1 stimulates glucose uptake in 3T3-LI adipocytes. In this report, we extend the studies to neonatal rat cardiomyocytes. ET-1, but not angiotensin-II (A-II), stimulated glucose uptake in a dose-dependent manner with an EC50 value at approximately 1 nM, and an approximately 2-fold stimulation at 100 nM. As a comparison, insulin stimulated glucose uptake in a dose-dependent manner with an EC50 value at 1 nM, and a 2.5-fold stimulation at 100 nM. Western blot analysis shows that ET-1 stimulated the translocation of insulin-responsive aminopeptidase (IRAP), an aminopeptidase in GLUT4 (glucose transporter)-containing vesicles, from the cytoplasm to the plasma membrane. The effect of ET-1 on glucose uptake was blocked by A-127722, an antagonist selective for the ET(A)-receptor. ET-1 treatment did not induce phosphorylation of insulin receptor-beta (IRbeta), insulin receptor substrate-1 (IRS-1) or Akt, but stimulated the phosphorylation of extracellular signal-regulated kinase (ERK1/2). The effect of ET-1 on glucose uptake was not inhibited by inhibitors for protein kinase C (PKC), protein kinase A (PKA) and phosphatidylinositol-3-kinase (PI3'-kinase). Our results show that ET-1 stimulates glucose uptake in neonatal rat cardiomyocytes via activation of the ET(A)-receptor.
Wu-Wong
J R
JR
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois, USA. ruth.r.wuwong@abbott.com
Berg
C E
CE
Kramer
D
D
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D019332:Endothelin-1 / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology*
D019332:Endothelin-1; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011518:Proto-Oncogene Proteins; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; C495694:Slc2a4 protein, rat; D000804:Angiotensin II; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose