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- Title
Coupling of Endogenous Glucose Production to Glucose Utilization During Exercise in the C57BI/6J Mouse.
- Authors
Li, Candice Y.; Ayala, Julio E.; Berglund, Eric D.; Fueger, Patrick T.; Lynes, Sara E.; Lee-Young, Robert S.; Wasserman, David H.
- Abstract
Despite the marked increase in muscle glucose utilization that occurs with exercise, blood glucose normally changes very little as endogenous glucose production increases proportionally. We tested the hypothesis that the increase in glucose production is stimulated during exercise by feedback resulting from increased glucose uptake by the working muscle. For this purpose, Glut4 knockout mice (G4KO) were compared to wild type C57B1/6J littermates (WT) during rest and exercise. Catheters were implanted in the carotid artery and jugular vein of 4 month old G4KO and WT mice (n=6/genotype). After 7 d, 5 h fasted mice were run on a treadmill at 12 m/min for 30 min. G4KO body weight (G4KO: 24±1, WT: 27±1 g) and sedentary plasma glucose (G4KO: 208±22, WT: 197±6 mg/dl) and insulin (G4KO: 0.5±0.13, WT: 0.7±0.02 ng/ml) were similar to WT. A primed infusion of [3-³H]glucose was given to determine endogenous glucose production (R[sub a] and clearance. During exercise, WT glucose clearance increased by 2-fold (124±1 to 20±4 ml/kg/min). This increase was completely abolished in G4KO (9±1 to 8±1 ml/kg/min). In WT, the increase in clearance corresponded to a 2-fold increase in R[sub a] (23±2 to 45±5 mg/kg/min). Despite the absence of an increase in clearance in G4KO, R[sub a] increased (18±3 to 43±4 mg/kg/min) in a manner similar to WT. The occurrence of equal increases in glucose production with no comparable change in clearance resulted in marked hyperglycemia in G4KO (G4KO: 351±12, WT: 225±12 mg/dl). In conclusion, the increase in endogenous glucose production that occurs with exercise does so independently of feedback related to the increase in extraction of glucose by the muscle. Thus the signal that couples liver glucose production to muscular work is distinct from classical feedback control.
- Subjects
GLUCOSE; EXERCISE; MICE; MUSCLES; MONOSACCHARIDES
- Publication
Diabetes, 2007, Vol 56, pA37
- ISSN
0012-1797
- Publication type
Article