Glucosamine inhibits angiotensin II-induced cytoplasmic Ca2+ elevation in neonatal cardiomyocytes via protein-associated O-linked N-acetylglucosamine

Am J Physiol Cell Physiol. 2006 Jan;290(1):C57-65. doi: 10.1152/ajpcell.00263.2005. Epub 2005 Aug 17.


We previously reported that glucosamine and hyperglycemia attenuate the response of cardiomyocytes to inositol 1,4,5-trisphosphate-generating agonists such as ANG II. This appears to be related to an increase in flux through the hexosamine biosynthesis pathway (HBP) and decreased Ca2+ entry into the cells; however, a direct link between HBP and intracellular Ca2+ homeostasis has not been established. Therefore, using neonatal rat ventricular myocytes, we investigated the relationship between glucosamine treatment; the concentration of UDP-N-acetylglucosamine (UDP-GlcNAc), an end product of the HBP; and the level of protein O-linked N-acetylglucosamine (O-GlcNAc) on ANG II-mediated changes in intracellular free Ca2+ concentration ([Ca2+]i). We found that glucosamine blocked ANG II-induced [Ca2+]i increase and that this phenomenon was associated with a significant increase in UDP-GlcNAc and O-GlcNAc levels. O-(2-acetamido-2-deoxy-D-glucopyranosylidene)-amino-N-phenylcarbamate, an inhibitor of O-GlcNAcase that increased O-GlcNAc levels without changing UDP-GlcNAc concentrations, mimicked the effect of glucosamine on the ANG II-induced increase in [Ca2+]i. An inhibitor of O-GlcNAc-transferase, alloxan, prevented the glucosamine-induced increase in O-GlcNAc but not the increase in UDP-GlcNAc; however, alloxan abrogated the inhibition of the ANG II-induced increase in [Ca2+]i. These data support the notion that changes in O-GlcNAc levels mediated via increased HBP flux may be involved in the regulation of [Ca2+]i homeostasis in the heart.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylglucosamine / metabolism*
  • Angiotensin II / pharmacology
  • Animals
  • Animals, Newborn
  • Calcium / metabolism
  • Calcium Signaling / drug effects*
  • Calcium Signaling / physiology
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Down-Regulation / drug effects
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology
  • Glucosamine / pharmacology*
  • Hexosamines / metabolism
  • Homeostasis / drug effects
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Thapsigargin / pharmacology
  • Up-Regulation / drug effects
  • Vasoconstrictor Agents / pharmacology


  • Enzyme Inhibitors
  • Hexosamines
  • Vasoconstrictor Agents
  • Angiotensin II
  • Thapsigargin
  • Glucosamine
  • Calcium
  • Acetylglucosamine