Long-chain polyunsaturated fatty acids and chemically induced diabetes mellitus: Effect of ω-6 fatty acids

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2003-02, Vol.19 (2), p.93-114
• Main Authors: Suresh, Y, Das, U.N
• Format: Article
• Language: English
• Subjects: alloxan; Alloxan - administration & dosage; Animals; antioxidants; Antioxidants - metabolism; Antioxidants - therapeutic use; Apoptosis - drug effects; Cell Survival - drug effects; Cells, Cultured; diabetes mellitus; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - prevention & control; Enzymes - drug effects; Fatty Acids, Omega-6 - administration & dosage; Fatty Acids, Omega-6 - blood; Fatty Acids, Omega-6 - therapeutic use; Fatty Acids, Unsaturated - administration & dosage; Fatty Acids, Unsaturated - blood; Fatty Acids, Unsaturated - therapeutic use; glucose; In Vitro Techniques; insulin; Insulinoma - pathology; Lipids - blood; Male; Pancreas - metabolism; Rats; Rats, Wistar; ω-6 fatty acids
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/S0899-9007(02)00856-0

We previously showed that prior oral supplementation of oils rich in ω-3, eicosapentaenoic acid and docosahexaenoic acid, and ω-6, γ-linolenic acid and arachidonic acid, can prevent the development of alloxan-induced diabetes mellitus in experimental animals. But the effect of individual fatty acids on chemically induced diabetes mellitus is not known. We report the results of our studies with ω-6 fatty acids. Alloxan-induced in vitro cytotoxicity and apoptosis in an insulin-secreting rat insulinoma cell line, RIN, was prevented by prior exposure of these cells to linoleic acid, γ-linolenic acid, and arachidonic acid (AA) but not to dihomo-γ-linolenic acid. Cyclo-oxygenase and lipoxygenase inhibitors did not block this protective action of AA. Prior oral supplementation with γ-linolenic acid and pre- and simultaneous treatments with AA prevented alloxan-induced diabetes mellitus. Even though pretreatment with linoleic acid and dihomo-γ-linolenic acid and simultaneous treatment with linoleic acid, γ-linolenic acid, and dihomo-γ-linolenic acid did not prevent the development of diabetes mellitus, the severity of diabetes was much less. The saturated fatty acid stearic acid and the monounsaturated fatty acid oleic acid were ineffective in preventing alloxan-induced diabetes mellitus. γ-Linolenic acid and AA not only attenuated chemically induced diabetes mellitus but also restored the antioxidant status to normal range in various tissues. Changes in the concentrations of various fatty acids of the phospholipid fraction of plasma that occurred as a result of alloxan-induced diabetes mellitus also reverted to normal in the AA-treated animals. These results suggest that polyunsaturated fatty acids can prevent chemically induced diabetes in experimental animals and attenuate the oxidant stress that occurs in diabetes mellitus.