278 G. PopjAK 



mean R.Q. is in the neighbourhood of 1 -5. The Qacid gives an approxi- 

 mate measure of the acetate uptake; it will be seen that insulin caused in 

 all cases an increase in the uptake of acetate as well as glucose and an 

 increase also in the Qoj. We interpret these respiratory data as indica- 

 ting net fat synthesis by these slices in a glucose and acetate medium, 

 a process which is dramatically stimulated by insulin in vitro. Inci- 

 dentally, with rat tissue we also get similar insulin effects in glucose 

 alone, but not in acetate alone. 



Now, in seeking for a possible mechanism for this in vitro insulin 

 effect, we have considered the possibility that, as Dr. Popjak indicated, 

 glycerol may, under some circumstances, be a rate-limiting factor in 

 fatty acid synthesis. We should not lose sight of the fact that the mam- 

 mary gland does more than carry on a very active fatty acid synthesis; 

 it synthesizes glycerides, a process which must occur even in vitro. 

 Thus under circumstances in which the supply of glycerol is critical, the 

 provision of glycerol, by favouring the formation of glycerides and thus 

 removing free fatty acids from the site of build-up and breakdown, 

 might indirectly result in a stimulation of their synthesis. 



Table II includes a comparison between the effects of glycerol and 

 of insulin on the lactating rat mammary gland slices metabolizing acetate 

 plus glucose. Glycerol is seen to exert a qualitatively similar effect 

 to insulin except that the increase in the R.Q. is not so marked. I 

 should not like to be too dogmatic about this, but since it is clear that 

 glycerol here is promoting fat synthesis by mammary gland slices, it 

 does seem worth considering whether part of the effect of insulin might 

 be to increase the supply of glycerol at some point in the metabolic 

 breakdown of glucose. It is known that in yeast fermentation there is a 

 mechanism by which glycerol is formed by the dismutation of triose- 

 phosphate. 



I would emphasize that this suggestion is purely speculative at the 

 present time; it is equally possible that insulin exerts its lipogenic action 

 by virtue of its ability to stimulate the utilization of carbohydrate for 

 the production of the energy necessary to drive the fatty-acid synthesis. 



REFERENCES 



Balmain, J. H., and Folley, S. J. (1951). Biochem. J., 49, 663. 



CowiE, A. T., Buncombe, W. G., Folley, S. J., French, T. H., Glascock, 



R. F., Massart, L., Peeters, G., and Popjak, G. (1951). Biochem. J., 



48, xxxix. 



Popjak: I think it is pertinent to comment that in thinking of fat 

 synthesis we should think of the whole molecule and not just of fatty 

 acids alone. 



Gurin: I think it is appropriate to mention some of the results Dr. 

 Brady and I obtained at Pennsylvania on the synthesis of long chain 

 fatty acids. We also get the insulin effect with liver slices, both with 

 regard to the incorporation of isotope into the fatty acids and into 

 cholesterol. We are inclined to think that the insulin effect is more 



