SATURATED FATTY ACIDS 35 



and associates^" likewise noted a stimulation of fat formation caused by 

 insulin in slices from lactating mammary gland from rat, rabbit, and mouse 

 as studied with C^* and tritium. Tritium was found to offer a more sensi- 

 tive method for the study of lipogenesis than did C^*. 



It is kno^^^l that the development of hyperglycemia in diabetes is largely 

 to be ascribed to the inability of the animal to convert carbohydrate to 

 fat. Stetten and Boxer^^'' were the first to demonstrate that the rat, when 

 rendered diabetic with alloxan, largely loses its capacity to utilize glucose 

 for hpogenesis. In their later work, Chernick and associates^^^ reported 

 that the conversion of C^Mabeled glucose to fatty acids was reduced to 

 practically zero in hver slices from alloxan-diabetic rats. However, when 

 the diabetic rats were pretreated with insulin for five days, the defect in 

 lipogenesis from carbohydrate was completely corrected, even in the case 

 of a rat which had suffered from diabetes for as long as 150 days.'^^^ 



The extent to which acetate and lactate are used for Hpogenesis in dia- 

 betes has been shown to be a function of the type of carbohydrate which is 

 simultaneously being metabohzed. Thus, Baker, Chaikoff, and Schusdek'" 

 reported that hepatic lipogenesis in liver slices from alloxan-diabetic rats 

 was greatly depressed when glucose was fed. In some cases, the extent of 

 fat formation was reduced to 10% of the normal. The livers of these rats 

 had almost completely lost their capacity to convert glucose to fatty acids. 

 In contradistinction to these results, the administration of fructose restored 

 the ability of the liver to convert acetate or lactate to fatty acids; however, 

 fructose could not correct the defective Hpogenesis observed in the pres- 

 ence of glucose. The action of fructose differs from that of insuHn in this 

 latter respect. Whereas insulin is able to restore the Hpogenic capacity of 

 the diabetic Hver completely, not only in the case of acetate and lactate 

 but also in that of glucose, fructose cannot function with the latter metab- 

 oHte. It is beHeved that fructose exerts its effect by affording a con- 

 tinuous source of metaboHtes for the glycolytic system; these may be re- 

 quired to maintain lipogenesis in the liver. 



InsuHn likewise promotes fat synthesis in mammary tissue. Several 

 investigators '58' '59 reported that crystalline insulin exerts a marked po- 

 tentiating effect upon fat synthesis in sHces of mammary tissue from 



1" J. H. Balmain, S. J. Follej', and R. F. Glascock, Nature, 168, 1083 (1951). 



1" De W. Stetten, Jr., and G. E. Bo.\er, /. Biol. Chem., 156, 271-278 (1944). 



"" S. S. Chernick, I. L. Chaikoff, E. J. Masoro, and E. Isaeff, /. Biol. Chem., 186, 527- 



"«S. S. Chernick and I. L. Chaikoff, /. Biol. Chem., 186, 535-542 (1950). 

 •"N. Baker, I. L. Chaikoff, and A. Schusdek, /. Biol. Chem., 194, 435-443 (1952). 

 15* J. H. Balmain, T. H. French, and S. J. FoUey, Nature, 165, 807-808 (1950). 

 "'J. H. Balmain and S. J. FoUey, Biochem. J., 49, 663-670 (1951). 



