Exercise-stimulated glucose turnover in the rat is impaired by glucosamine infusion

Abstract

The infusion of glucosamine causes insulin resistance, presumably by entering the hexosamine biosynthetic pathway; it has been proposed that this pathway plays a role in hyperglycemia-induced insulin resistance. This study was 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-GlcN 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 infusion 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 ∼2.2-fold from 46 ± 2 to 101 ± 5 μmol · 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 control in the low-GlcN group (47 ± 2 to 90 ± 3 μmol · kg-1 · min-1; P < 0.01) and 72% of control in the high-GlcN group (43 ± 1 to 73 ± 3 μmol · kg-1 · min-1; P < 0.01). Similarly, the metabolic clearance rate (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 MCR 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 glucosamine infusion nor exercise significantly affected plasma insulin or free fatty acid (FFA) concentrations. In conclusion, the infusion of glucosamine, which is known to cause insulin resistance, also impaired exercise-induced glucose uptake. This inhibition was independent of hyperglycemia and FFA levels.