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 (highGlcN 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 highGlcN 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. Diabetes 50:139-142, 2001 C hronic hyperglycemia is the cardinal metabolic feature of diabetes and can adversely affect glucose homeostasis by interfering with insulin action and/or ␤-cell function (1). Studies in humans have shown that experimental hyperglycemia or diabetesassociated hyperglycemia can cause insulin resistance or exacerbate an underlying insulin-resistant state (2). This finding is supported by animal and in vitro studies that directly show that hyperglycemia can cause impaired insulin action in vitro and insulin resistance in vivo (1,3,4).The mechanism by which hyperglycemia causes insulin resistance remains incompletely understood, but several studies have implicated the hexosamine biosynthesis pathway (5-8). This hypothesis holds that hyperglycemia, by way of mass action, leads to increased flux of glucose carbons through the hexosamine pathway (9). This occurs by glutamine:fructose-6-phosphate amidotransferase (GFAT)-mediated conversion of fructose-6-phosphate (F6P) to glucosamine-6-phosphate (G6P), with subsequent metabolism of G6P through the hexosamine pathway. Distal metabolic products of this pathway in some way may lead to decreased insulin-stimulated GLUT4 translocation and subsequent red...

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

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Effect of glucosamine supplementation on fasting and non-fasting plasma glucose and serum insulin concentrations in healthy individuals

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Putative Anti-Immobility Action of Acute Insulin Is Attributable to an Increase in Locomotor Activity in Healthy Wistar Rats

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