Fatty Acid Desaturation in Experimental Diabetes Mellitus

Abstract

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.

Relationship between fatty acids and the endocrine and neuroendocrine system

“…Insulin plays an important role in desaturation. Insulin treatment in humans (Tilvis et al 1986;el Boustani et al 1989) as well as experimental diabetic animals (Gellhorn and Benjamin 1964;Eck et al 1979;Prasad and Joshi 1979) stimulates desaturases. Eck et al (1979) reported that Table II.…”

Polyunsaturated Fatty Acids: Biochemical, Nutritional and Epigenetic Properties

“…In experimental diabetes and in spontaneously diabetic rats, there are reduced activities of ⌬-9, ⌬-6, and ⌬-5 liver microsomal desaturases, which are restored after insulin treatment [65,66].…”

Effect of Induced Acute Diabetes and Insulin Therapy on Stratum Corneum Barrier Function in Rat Skin

“…Insulin is well known for its stimulatory effect on cell proliferation [22] particularly for keratinocytes [23,24]. Further, insulin will increase 14 C-acetate incorporation into polyunsaturated fatty acids of skin [25] and increase fatty acid desaturase activity [20]. Thus, the response observed in the permeability kinetics of the insulin-treated diabetic rats may be from a hyperproliferation response or a further lipid imbalance in the stratum corneum lamella.…”

“…This suggests that the insulin is having an independent effect on the epidermis beyond the systemic regulation of carbohydrate metabolism. Potentially, the epidermis may have experienced an overexposure of insulin, as a long-acting form was used (protamine zinc) which was administered at a relatively high dose [20]. Consequently, skin insulin levels may have been very different from what would typically be received from normal nondiabetic systemic circadian levels expected in normal rodents [21].…”