Linoleic acid metabolism in the spontaneously diabetic rat:: Δ6-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 of liver microsomal Delta6-desaturase of spontaneously diabetic BioBreeding/Edinburgh rats receiving subcutaneous insulin daily and of genetically related nondiabetic animals. The activity of Delta6-desaturase was then compared with indices of activity (plasma lipid fatty acid product/precursor ratios) frequently used in human studies. Diabetic rats treated with insulin had 75 +/- 8% of the activity of microsomal Delta6-desaturase of nondiabetic controls (P < 0.05). insulin withdrawal tended to reduce the activity further (61% of control), although the activity did not differ from insulin-treated diabetic rats. The ratio of plasma phospholipid or cholesteryl ester <gamma>-linolenic over linoleic acid was not decreased in insulin-treated diabetic 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 activity gave inconsistent results in insulin-deprived rats. The ratio of gamma -linolenic over linoleic acid of cholesteryl esters did not differ between control and diabetic rats, nor did it correlate with microsomal Delta6-desaturase activity. Furthermore, the index of Delta6-desaturase activity, derived from the fatty acid composition of microsomal phospholipids, did not correlate with microsomal Delta6-desaturase activity. Diabetes, even when controlled by regular insulin injections, reduces the metabolism of linoleic acid, but the effect is less than previously published. The fatty acid compositions of plasma and liver microsomal lipids are not reliable indices of Delta6-desaturase activity in diabetes.