title: Glucosamine-supplementation promotes endoplasmic reticulum stress, hepatic steatosis and accelerated atherogenesis in apoE-/- mice.
abstract: OBJECTIVE
  To determine the effects of glucosamine-supplementation on endoplasmic reticulum (ER) stress levels and atherogenesis, and to investigate the potential role of glucosamine in hyperglycemia-associated accelerated atherosclerosis.
  
  
  METHODS
  Five week old apolipoprotein E-deficient (apoE-/-) mice were provided with normal drinking water or water supplemented with 5% glucosamine (w/v) or 5% mannitol (w/v). To induce hyperglycemia, a separate group of apoE-/- mice received multiple low dose injections of streptozotocin (STZ). All mice were provided with a standard chow diet and were euthanized at 15 weeks of age. Hepatic and vascular ER stress levels and atherosclerotic lesion area at the aortic root were determined.
  
  
  RESULTS
  STZ-induced hyperglycemic and glucosamine-supplemented mice had significantly larger and more advanced atherosclerotic lesions than control mice. Indications of ER stress were increased in the livers and atherosclerotic lesions of hyperglycemic and glucosamine-supplemented mice but not in the controls. In glucosamine-supplemented mice accelerated atherosclerosis was independent of detectable changes in blood glucose concentration, glucose tolerance, plasma insulin, or plasma lipid levels.
  
  
  CONCLUSIONS
  Similar to hyperglycemia, glucosamine-supplementation promotes ER stress, hepatic steatosis and accelerated atherosclerosis. These findings support a model by which hyperglycemia promotes hepatic and vascular complications via a glucosamine intermediate.
authors.affiliation: Thrombosis and Atherosclerosis Research Institute, McMaster University, 237 Barton Street East, Hamilton, Ontario, Canada, L8L 2X2. dan.beriault@taari.ca
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Beriault
authors.forename: Suparna
authors.initials: S
authors.lastname: Sharma
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shi
authors.forename: Mohammad I
authors.initials: MI
authors.lastname: Khan
authors.forename: Geoff H
authors.initials: GH
authors.lastname: Werstuck
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000139:chemically induced* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D005234:Fatty Liver / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D005944:Glucosamine / Q000633:toxicity*; D006943:Hyperglycemia / Q000150:complications* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D013311:Streptozocin; D056811:Unfolded Protein Response
chemical_list: D001057:Apolipoproteins E; D013311:Streptozocin; D005944:Glucosamine