title: Mechanisms of enhanced insulin sensitivity in endurance-trained athletes: effects on blood flow and differential expression of GLUT 4 in skeletal muscles.
abstract: Exercise is associated with increased insulin sensitivity. To better understand mechanisms that could be responsible for this association, we studied seven controls and seven endurance-trained athletes. A 600 mU/m2.min hyperinsulinemic euglycemic glucose clamp with the limb balance technique assessed insulin sensitivity as whole body glucose uptake (WBGU) and leg glucose uptake (LGU). Indirect calorimetry and hemodynamic measurements, such as leg blood flow (LBF) and cardiac output, were performed at baseline and maximal insulin stimulation. The content of the glucose transporter GLUT 4 and muscle fiber type were evaluated in three muscle groups: vastus lateralis, gastrocnemius, and biceps. Athletes exhibited 35% higher WBGU and 30% higher LGU than controls. Basal LBF (liters per min) was higher in athletes, but the difference was not statistically significant. After insulin stimulation, LBF was 31% higher in athletes than controls (P = 0.05). Indirect calorimetry revealed that athletes had a 44% higher rate of nonoxidative glucose metabolism than controls (P = 0.01). GLUT 4 levels in vastus were 90% (P < 0.05) greater in athletes, whereas smaller differences were noted between athletes and controls in biceps and gastrocnemius. Importantly, the vastus lateralis GLUT 4 content was correlated with WBGU (r = 0.60; P < 0.05) and LGU (r = 0.62; P < 0.05). Relative numbers of oxidative fibers were increased in vastus from athletes and were positively correlated with maximal oxygen consumption (VO2 max), but GLUT 4 content could not be correlated with oxidative fiber content in individual controls or athletes. We conclude that in humans 1) endurance training enhances insulin's ability to increase LBF; 2) GLUT 4 is differentially expressed as a function of muscle group and is up-regulated by exercise in a muscle-specific manner; 3) in vastus lateralis, GLUT 4 levels are well correlated with insulin-stimulated rates of both WBGU and LGU; and 4) GLUT 4 content and in vivo insulin sensitivity do not vary as a function of fiber type composition. Thus, blood flow and GLUT 4 expression in muscle are important mechanisms that mediate greater insulin sensitivity in athletes.
authors.affiliation: Department of Pediatrics, University of Texas Medical School, Houston 77030, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Hardin
authors.forename: B
authors.initials: B
authors.lastname: Azzarelli
authors.forename: J
authors.initials: J
authors.lastname: Edwards
authors.forename: J
authors.initials: J
authors.lastname: Wigglesworth
authors.forename: L
authors.initials: L
authors.lastname: Maianu
authors.forename: G
authors.initials: G
authors.lastname: Brechtel
authors.forename: A
authors.initials: A
authors.lastname: Johnson
authors.forename: A
authors.initials: A
authors.lastname: Baron
authors.forename: W T
authors.initials: WT
authors.lastname: Garvey
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D015309:Glucose Clamp Technique; D051275:Glucose Transporter Type 4; D006019:Glycolysis / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D010807:Physical Endurance; D012016:Reference Values; D012039:Regional Blood Flow; D012044:Regression Analysis; D012420:Running; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D005230:Fatty Acids, Nonesterified; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495692:SLC2A4 protein, human; D009638:Norepinephrine