Acute glucosamine-induced insulin resistance in muscle in vivo is associated with impaired capillary recruitment

Aims/hypothesis: 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. Materials and 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. Conclusion/interpretation: 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. © Springer-Verlag 2005.