Fatty acid desaturation in experimental diabetes mellitus.
Microsomal fatty acid desaturation is defective in streptozotocin-induced experimental diabetes. This defect is correctable by insulin treatment. The electron transport chain needed for microsomal fatty acid desaturation was studied in liver microsomes of streptozotocin diabetic rats, and the defect was localized to the terminal desaturase enzyme. Cytochrome b5 levels were elevated in the face of decreased fatty acid desaturation and returned to normal after 48 h of insulin treatment; 2 U of regular insulin every 6 h for 24 h repaired the fatty acid desaturation defect, while 0.5 U failed to correct the defect. Both the delta 6 and delta 9 desaturase defects (linoleic acid and stearoyl-CoA desaturation) required similar amounts of insulin and periods of time for correction, although these are different enzymes. This is consistent with the desaturation defect being due to a protein synthetic effect. Diabetic rats treated twice daily with injections of 4 U of NPH insulin showed a "super" repair of their desaturase defect by 48 h: delta 9 desaturase activity increased eight times over control activity, while delta 6 desaturase activity increased two and one-half times over control activity. This, together with the fact that delta 6 desaturase activity in diabetes (64% of control) is altered less than is delta 9 desaturase activity (22% of control), indicates that delta 6 desaturase enzyme activity is less responsive to insulin than is delta 9 desaturase enzyme activity. The physiologic significance of altered fatty acid desaturation in diabetes mellitus is unknown.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004579:Electron Transport; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D051381:Rats
D001786:Blood Glucose; D003580:Cytochromes; D007328:Insulin; D012313:RNA; D004247:DNA; D007770:L-Lactate Dehydrogenase; D044943:Fatty Acid Desaturases