The Effect of Insulin on the Meta- Bolism of the Perfused in Situ Rat Lung

The metabolic potential of the lung has been generally unrecognized. As this organ receives half the cardiac output, small changes in its metabolism could have profound effects on whole body fuel homeostatis. The lung has previously been considered to be unresponsive to insulin (Moxley & Longmore, 1975, Life Sciences. 17, 921). We have reexamined the effects of insulin using an improved in situ whole organ preparation. The lungs from fed or 48 h starved male Wistar rats were perfused through pulmonary artery and left atrial cannulae with Krebs-Henseleit buffer containing albumin,4 mmoll-' glucose and insulin 50 mU I-', where appropriate. Perfusate samples were taken at 30 min intervals for 4 h and analysed for glucose, lactate, pyruvate, alanine and glycerol. At 30 min, metabolite concentrations were similar with or without prior addition of insulin. Subsequently, insulin increased glucose uptake and lactate release. At 4 h the mean (i SEM) glucose uptake was 57 f 3 and 74 f 6 -01 g dry wt-' h-' (P< 0.05) and the lactate production 76 f 4 and 98 i 1 pmol g dry wt-' h-' (P< 0.01) without and with insulin respectively. Insulin caused a small significant increase in glycerol production but had no effect on other metabolites. Similar effects were noted when the insulin concentration was increased to 500 mU I-'. In the fasted animal, the lower dose of insulin had no effect on glucose metabolism but with higher concentrations a similar increase to that found for the fed animal was noted. This in situ lung perfusion technique offers advantages over previous methods. There was no evidence of cellular damage histologically and the dry wt/wet wt ratio was similar to that of the unperfused lung. It is technically simple, thus minimizing ischaemic damage; the myocardium cannot contribute metabolites to the perfusate; it produces physiological flow rates; and pulmonary oedema is avoided. The demonstration of an effect of insulin suggests that this organ may have a non-respiratory metabolic influence on the body not hitherto recognized.