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Insulin resistance and substrate utilization in human endotoxemia.
A O Agwunobi1, C Reid, P Maycock
1Medical Research Council Trauma Group, North West Injury Research Center, University of Manchester, Hope Hospital, Salford, United Kingdom.
The Journal of Clinical Endocrinology and Metabolism
|November 4, 2000
Summary
Bacterial lipopolysaccharide (LPS) administration in healthy volunteers induced insulin resistance, mimicking sepsis. This response impaired glucose utilization, primarily through reduced nonoxidative disposal, offering a human model for critical illness research.
Area of Science:
- Metabolic Medicine
- Human Physiology
- Immunology
Background:
- Infection triggers insulin resistance, but its mechanisms remain unclear.
- Bacterial lipopolysaccharide (LPS) is used to model infection's inflammatory effects.
- LPS's direct impact on human insulin resistance requires investigation.
Purpose of the Study:
- To determine if LPS administration induces insulin resistance in humans.
- To assess LPS effects on insulin sensitivity and substrate utilization.
- To establish LPS as a human model for sepsis-induced insulin resistance.
Main Methods:
- Paired cross-over studies in healthy volunteers (n=6).
- Administered Escherichia coli endotoxin (LPS) or saline control.
- Utilized a 10-hour euglycemic hyperinsulinemic clamp.
Main Results:
- LPS induced fever, tachycardia, and hypotension.
- Initial glucose utilization increased, followed by progressive decline, indicating insulin resistance by 420 minutes.
- Impaired nonoxidative glucose disposal, not glucose oxidation, was responsible for reduced glucose utilization.
- Cortisol and Growth Hormone (GH) responses correlated with observed insulin resistance.
Conclusions:
- LPS administration in humans replicates key metabolic responses seen in sepsis.
- LPS induces significant insulin resistance, primarily affecting nonoxidative glucose metabolism.
- This study validates LPS as a valuable human model for investigating insulin resistance in critical illness.