Feb 3, 2007

Intermittent hypoxia causes insulin resistance in lean mice independent of autonomic activity

American Journal of Respiratory and Critical Care Medicine
Nao IiyoriChristopher P O'Donnell


Although many clinical physiology and epidemiology studies show an association between obstructive sleep apnea (OSA) and markers of insulin resistance, no causal pathway has been established. The purpose of the current study was to determine if the intermittent hypoxia (IH) stimulus that characterizes OSA causes insulin resistance in the absence of obesity. Furthermore, we assessed the impact of IH on specific metabolic function in liver and muscle. Finally, we examined the potential mechanistic role of the autonomic nervous system (ANS) in mediating insulin resistance in response to IH. Hyperinsulinemic euglycemic clamps were conducted and whole-body insulin sensitivity, hepatic glucose output, and muscle-specific glucose utilization assessed in conscious, chronically instrumented adult male C57BL/6J mice exposed to (1) IH (achieving a nadir of Fi(O(2)) = 5-6% at 60 cycles/h for 9 h), (2) intermittent air as a control, (3) IH with ANS blockade (hexamethonium), or (4) IA with ANS blockade. IH decreased whole-body insulin sensitivity compared with intermittent air (38.8 +/- 2.7 vs. 49.4 +/- 1.5 mg/kg/min, p < 0.005) and reduced glucose utilization in oxidative muscle fibers, but did not cause a change in hepatic glucose output. ...Continue Reading

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Mentioned in this Paper

Autonomic Nervous System Disorders
Metabolic Process, Cellular
Biochemical Pathway
Insulin Sensitivity
Clinical Physiology
Glucose, (beta-D)-Isomer
Insulin Resistance
Hyperinsulinemic Hypoglycemia, Familial, 1
Body Mass Index Procedure

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