This study evaluated
lactate disposal via gluconeogenesis as well as effects of FFA availability on gluconeogenesis via
pyruvate (GNG(PYR)) in patients with
mitochondrial myopathy due to complex I deficiency (CID). The rates of GNG(PYR) were measured in three CID patients and six healthy controls at rest and during 90 min cycle exercise, using the
deuterium-labeled water method. All subjects served as their own control: on one occasion they were studied in the fasting state, and on the second occasion they received an infusion of
triacylglycerol plus
heparin. At rest, the fractional rate of gluconeogenesis from
pyruvate was higher in patients than in controls in the fasting state.
Triacylglycerol infusion was associated with increased rates of GNG(PYR) at rest in controls (p < 0.05) but not in patients. Circulating
lactate and
pyruvate levels were increased 3-fold during exercise in the CID patients. During exercise, GNG(PYR) increased in the CID patients (p < 0.01) and remained unchanged in controls, resulting in 85% and 72% higher absolute rates of GNG(PYR) in the patients than in the controls during fasting and
triacylglycerol infusion, respectively. During exercise, rates of GNG(PYR) were not different between fasting and
triacylglycerol infusion within both groups. Our data show that 1) GNG(PYR) is increased during exercise in CID patients; 2) increased
pyruvate availability contributes to the higher rates of GNG(PYR) in the CID patients; and 3) exogenous infusion of
fatty acids is not associated with increased rates of GNG(PYR) in CID patients at rest or during exercise. GNG(PYR) is a significant mechanism of
lactate disposal in exercising CID patients, but
triglyceride infusion does not enhance their
lactate disposal through this mechanism.