This study investigates the effect of acute, physiological elevations in plasma free fatty acid (FFA) concentrations on glucose production and utilization in normal subjects under three controlled experimental conditions. The first condition, euglycemic hyperinsulinemia (Group A), involves raising plasma insulin levels by 100 μU/ml while maintaining fasting glucose levels. In this condition, lipid infusion significantly inhibits total glucose uptake, and endogenous glucose production is completely suppressed. The second condition, hyperglycemic hyperinsulinemia (Group B), involves raising plasma glucose levels by 125 mg/100 ml while maintaining high insulin levels. Lipid infusion in this condition also impairs glucose utilization, and endogenous glucose production is again inhibited. The third condition, hyperglycemia with basal insulin levels (Group C), involves raising plasma glucose levels by 200 mg/100 ml while maintaining low insulin levels. Lipid infusion in this condition has no effect on glucose uptake but significantly increases endogenous glucose production. The study concludes that in the well-insulinized state, elevated FFA levels effectively compete with glucose for uptake by peripheral tissues, regardless of the presence of hyperglycemia. However, when insulin is deficient, elevated rates of lipolysis may contribute to hyperglycemia through an enhancement of endogenous glucose output rather than competition for fuel utilization.This study investigates the effect of acute, physiological elevations in plasma free fatty acid (FFA) concentrations on glucose production and utilization in normal subjects under three controlled experimental conditions. The first condition, euglycemic hyperinsulinemia (Group A), involves raising plasma insulin levels by 100 μU/ml while maintaining fasting glucose levels. In this condition, lipid infusion significantly inhibits total glucose uptake, and endogenous glucose production is completely suppressed. The second condition, hyperglycemic hyperinsulinemia (Group B), involves raising plasma glucose levels by 125 mg/100 ml while maintaining high insulin levels. Lipid infusion in this condition also impairs glucose utilization, and endogenous glucose production is again inhibited. The third condition, hyperglycemia with basal insulin levels (Group C), involves raising plasma glucose levels by 200 mg/100 ml while maintaining low insulin levels. Lipid infusion in this condition has no effect on glucose uptake but significantly increases endogenous glucose production. The study concludes that in the well-insulinized state, elevated FFA levels effectively compete with glucose for uptake by peripheral tissues, regardless of the presence of hyperglycemia. However, when insulin is deficient, elevated rates of lipolysis may contribute to hyperglycemia through an enhancement of endogenous glucose output rather than competition for fuel utilization.