title: Acute glucosamine-induced insulin resistance in muscle in vivo is associated with impaired capillary recruitment.
abstract: OBJECTIVE
  Glucose toxicity and glucosamine-induced insulin resistance have been attributed to products of glucosamine metabolism. In addition, endothelial cell nitric oxide synthase is inhibited by glucosamine. Since insulin has endothelial nitric-oxide-dependent vasodilatory effects in muscle, we hypothesise that glucosamine-induced insulin resistance in muscle in vivo is associated with impaired vascular responses including capillary recruitment.
  
  
  METHODS
  Glucosamine (6.48 mg kg(-1) min(-1) for 3 h) was infused with or without insulin (10 mU kg(-1) min(-1)) into anaesthetised rats under euglycaemic conditions.
  
  
  RESULTS
  Glucosamine infusion alone increased blood glucosamine (1.9+/-0.1 mmol/l) and glucose (5.4+/-0.2 to 7.7+/-0.3 mmol/l) (p<0.05) but not insulin. Glucosamine induced both hepatic and muscle insulin resistance as evident from measures of glucose appearance and disposal as well as hind-leg glucose uptake, which was inhibited by approx. 50% (p<0.05). Insulin-mediated increases in femoral arterial blood flow and capillary recruitment were completely blocked by glucosamine.
  
  
  CONCLUSIONS
  Glucosamine mediates a major impairment of insulin action in muscle vasculature associated with the insulin resistance of muscle. Further studies will be required to assess whether the impaired capillary recruitment contributes to insulin resistance.
authors.affiliation: Biochemistry, School of Medicine, University of Tasmania, Private Bag 58, Hobart, Tasmania 7001, Australia.
authors.forename: M G
authors.initials: MG
authors.lastname: Wallis
authors.forename: M E
authors.initials: ME
authors.lastname: Smith
authors.forename: C M
authors.initials: CM
authors.lastname: Kolka
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: S M
authors.initials: SM
authors.lastname: Richards
authors.forename: S
authors.initials: S
authors.lastname: Rattigan
authors.forename: M G
authors.initials: MG
authors.lastname: Clark
mesh_terms: D000465:Algorithms; D000818:Animals; D002196:Capillaries / Q000187:drug effects; D005263:Femoral Artery / Q000187:drug effects; D005944:Glucosamine / Q000097:blood / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000097:blood / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000502:physiology; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D014969:Xanthine Oxidase; D005944:Glucosamine