Arachidonic acid deficiency in streptozotocin-induced diabetes.

Abstract

Fatty acid compositions of phospholipids of heart, liver, kidney, aorta, and serum from rats having streptozotocininduced diabetes were determined and compared with those of nondiabetic controls. Linoleic and dihomo-y-linolenic acids were increased whereas arachidonic acid was decreased in most tissues, suggesting an impairment of A5-desaturase activity. Acids derived from linolenic acid were increased in some diabetic tissues from diabetic animals although the linolenic content was normal, indicating less impairment in the desaturation of the w3 series of fatty acids. Diabetes suppressed all polyunsaturated acids in the whole animal, but the competition between w3 and w6 acids favored the excessive suppression of long-chain w6a acids and an increase in the proportion of w3 acids in lipids of vital tissues. These changes in fatty acid composition of the phospholipids may have significant effects on cellular functions and vasoregulatory control mechanisms in diabetes.Involvement of essential fatty acids (EFA) in diabetes was suggested by the observation that alloxan-induced diabetes accelerated and intensified symptoms of EFA deficiency (1). Changes in fatty acid composition have been reported in both humans (2-4) and animals with diabetes (5)(6)(7)(8). Decreased arachidonic acid in serum is correlated with hyperglycemia (2, 3) and with increased clinical complications. In diabetic rats, decreased arachidonic, palmitoleic, and oleic acids and increased linoleic and docosahexaenoic acids have been found in liver microsomal lipids (8). Conversely, diabetic rats fed an EFA-deficient diet manifest fewer biochemical changes and a higher level of arachidonic acid than do nondiabetic EFA-deficient controls (9). Many changes in fatty acid patterns of diabetic tissues can also result from dietary changes because mammalian cells require exogenous precursors of the long-chain polyunsaturated fatty acids (PUFA) (10, 11). Linoleic acid (18:2w6) § and y-linolenic acid (18:3w3) are the precursors of the w6 and w3 families of PUFA, which are important structural components of tissue lipids, which in turn are precursors of prostaglandins (PGs) and other products of PUFA oxidation important in the regulation of metabolism.This report describes the fatty acid composition of phospholipids (PLs) from several organs of rats made diabetic by streptozotocin, emphasizing the fatty acids of the w6 and w3 series, both known to be essential in humans (11). These two families of PUFA have parallel pathways of metabolism leading to different vasoactive substances (12), which may be related to the pathogenesis of diabetic vascular disease (13,14 In experiment 1, diabetic rats and age-matched nondiabetic controls were fed the chow diet throughout the study to assay whether diabetes influenced the PUFA pattern of rats on a standard rat ration composed of natural feedstuffs. The rats were made diabetic at 49 days of age and killed after 61 days of diabetes. Samples of heart, serum, liver, whole kidney, and abdominal aorta were analyzed.I...

Glucose oversupply increases Δ9-desaturase expression and its metabolites in rat skeletal muscle

“…These data are in accordance with recent reports showing decreased elongase activity (increased C16:0 on the costs of C18:0) in muscle of healthy subjects made insulin resistant [7]. In obesity and insulin resistance states, ∆5-desaturase activity was reported to be reduced [4,16,52,54], whereas that of ∆6-desaturase increased [16]. We found little change in ∆5-desaturase and no change in ∆6-desaturase activity indices.…”

“…Previous reports have indicated that elongase activity (18:0/16:0) is reduced in insulin resistance [16,50,52,53]. In this study, we found that elongase activity was decreased in day 5 as assessed by the activity indices found in triglycerides and diglycerides fractions.…”

Improvement of diabetic control by continuous subcutaneous insulin infusion therapy changes fatty acid composition of serum lipids and erythrocytes in Type 1 (insulin-dependent) diabetes

“…GLNA is further converted to DHGLA by chain elongation and further by the A 5 desaturase to arachidonic acid. The activities of these enzymes are decreased in experimental insulin deficiency [4][5][6][7][8][9][10]. In the present study the contents of DHGLA and arachidonic acid were slightly increased in serum lipids and especially in erythrocytes of the diabetic patients proportionately to the decrease in glycosylated haemoglobin.…”

“…The initial and rate-controlling step in the conversion of linoleic acid to arachidonic acid is the formation of 7/-linolenic acid (GLNA 18: 3,n-6) by the A6 desaturase enzyme [4][5][6][7][8][9][10]. GLNA is further converted to DHGLA by chain elongation and further by the A 5 desaturase to arachidonic acid.…”

“…As compared to serum triglyceride and cholesterol levels and lipoprotein metabolism, relatively little attention has been paid to the fatty acid composition of serum lipids and blood cell membranes in human Type 1 (insulin-dependent) diabetes. However, both human studies [1][2][3] and animal experiments [4][5][6][7][8][9][10] have indicated that the insulin deficit may affect the metabolism of essential fatty acids. The conversion of essential fatty acids like linoleic acid (18:2,n-6) to longer-chain polyunsaturated fatty acids (PUFA), e.g.…”