Linoleic acid metabolism in the spontaneously diabetic rat: Delta 6-desaturase activity vs. product/precursor ratios

The activity of Delta6-desaturase of linoleic acid, a rate-limiting step in the formation of arachidonic acid, is decreased in animal models of severe , uncontrolled diabetes. The aim of the study was to measure the activity o f liver microsomal Delta6-desaturase of spontaneously diabetic BioBreeding/ Edinburgh rats receiving subcutaneous insulin daily and of genetically rela ted nondiabetic animals. The activity of Delta6-desaturase was then compare d with indices of activity (plasma lipid fatty acid product/precursor ratio s) frequently used in human studies. Diabetic rats treated with insulin had 75 +/- 8% of the activity of microsomal Delta6-desaturase of nondiabetic c ontrols (P < 0.05). insulin withdrawal tended to reduce the activity furthe r (61% of control), although the activity did not differ from insulin-treat ed diabetic rats. The ratio of plasma phospholipid or cholesteryl ester <ga mma>-linolenic over linoleic acid was not decreased in insulin-treated diab etic rats. By contrast, the ratio of gamma -linolenic over linoleic acid of microsomes was almost threefold higher in insulin-treated diabetic rats (P < 0.05). The <gamma>-linolenic over linoleic acid ratio as an index of act ivity gave inconsistent results in insulin-deprived rats. The ratio of gamm a -linolenic over linoleic acid of cholesteryl esters did not differ betwee n control and diabetic rats, nor did it correlate with microsomal Delta6-de saturase activity. Furthermore, the index of Delta6-desaturase activity, de rived from the fatty acid composition of microsomal phospholipids, did not correlate with microsomal Delta6-desaturase activity. Diabetes, even when c ontrolled by regular insulin injections, reduces the metabolism of linoleic acid, but the effect is less than previously published. The fatty acid com positions of plasma and liver microsomal lipids are not reliable indices of Delta6-desaturase activity in diabetes.