Substrate utilization by the lung

Intermediary metabolism of the lung and its regulation have received relatively little attention in the past, partly because of difficulty in producing suitable models for study. An in situ perfused rat lung preparation is described which remains viable for four hours or more. Concentration-dependent glucose utilization has been found with this model, associated with marked lactate production. More than half the glucose used appears as lactate, despite the high PO2 and maintenance of normal ATP concentrations. The high rates of glycolysis may be related to glycerol-3-phosphate requirements for lipid synthesis. Glucose clearance from the perfusion medium is dependent on nutritional status, clearance by lungs from 48-hour starved animals being decreased by comparison with lungs of fed controls. Lactate is taken up actively at concentrations of 2 mmol/l or above but is produced at an initial lactate concentration of 0.4 mmol/l. Non-esterified fatty acids (1 mmol/l in the perfusate) are also cleared by lung and may be important as an energy source even though 80% is used for synthetic reactions. Alanine, glycerol and 3-hydroxybutyrate are unimportant as substrates. The lung responds to metabolically important hormones. Insulin and adrenaline cause an acute increase in glucose utilization whereas corticosterone and noradrenaline are inhibitory. Utilization of glucose is also diminished in lungs from diabetic ketoacidotic rats. Further work is required to establish the relative importance of oxidative and synthetic routes for added substrates and the mechanisms of hormonal regulation.