Exercise-stimulated glucose turnover in the rat is impaired by glucosamineinfusion

The infusion of glucosamine causes insulin resistance, presumably by enteri ng the hexosamine biosynthetic pathway; it has been proposed that this path way plays a role in hyperglycemia-induced insulin resistance. This study wa s undertaken to determine if glucosamine infusion could influence exercise- stimulated glucose uptake. Male SD rats were infused with glucosamine at 0. 1 mg kg(-1) . min(-1) (low-GlcN group), 6.5 mg . kg(-1) . min(-1) (high-Glc N group), or saline (control group) for 6.5 h and exercised on a treadmill for 30 min (17 m/min) at the end of the infusion period. Glucosamine infusi on caused a modest increase in basal glycemia in both experimental groups, with no change in tracer-determined basal glucose turnover. During exercise , glucose turnover increased similar to2.2-fold from 46 +/- 2 to 101 +/- 5 mu mol . kg(-1) . min(-1) in the control group. Glucose turnover increased to a lesser extent in the glucosamine groups and was limited to 88% of cont rol in the low-GlcN group (47 +/- 2 to 90 +/- 3 mu mol . kg(-1) . min(-1); P < 0.01) and 72% of control in the high-GlcN group (43 +/- 1 to 73 +/- 3 < mu>mol . k(-1) . min(-1); P < 0.01). Similarly, the metabolic clearance rat e (MCR) in the control group increased 72% from 6.1 +/- 0.2 to 10.5 +/- 0.7 ml . kg(-1) . min(-1) in response to exercise. However, the increase in MC R was only 83% of control in the low-GlcN group (5.2 +/- 0.5 to 8.7 +/- 0.5 ml . kg(-1) . min(-1); P < 0.01) and 59% of control in the high-GlcN group (4.5 +/- 0.2 to 6.2 +/- 0.3 ml . kg(-1) . min(-1); P < 0.01). Neither gluc osamine infusion nor exercise significantly affected plasma insulin or free fatty acid (FFA) concentrations. In conclusion, the infusion of glucosamin e, which is known to cause insulin resistance, also impaired exercise-induc ed glucose uptake. This inhibition was independent of hyperglycemia and FFA levels.