The Study On Relation Of α-Linolenic Acid And Insulin Resistance

Objective: To learn the effect and possible mechanism of a -linolenic acid on insulin resistance, and provide the theory basis for applying the plant oil richen a -linolenic acid in preventing and treating diabetes. Methods: ?A high-fat diet containing saturated fatty acids (lard oil) or monounsaturated fatty acids (teaseeds oil) or a -linolenic acid (perilla oil) given for 4wk to 5-wk-old Wistar rats (56.6% of calories as fat), lard oil group as positive group, normal group (low fat ) as negative control , made the mode rats of insulin resistance successfully after four weeks feeding. Compairing the insulin sensitive and the level of body fat> blood lipid -, skeletal muscles TG > glycogen in liver and skeletal muscles > fructose-1,6-bisphosphatase from liver using insulin tolerance test and enzyme chemical calorimetric analysis, and detecting the uncouple protein-1 mRNA level in brown fat -, G1UT4 mRNA level in white fat and skeletal muscles by half quantitative RT-PCR; (2) Detecting the effect of a -linolenic acid on protein kinase B signal conduction and expression of GLUT4 protein in skeletal muscles using primary cell culture -, immunocyto(histo)chemistry Western blot techniques, and compared with palmitic acid > oleic acid. Results: ?Compared with normal group, the ratio of glucose decline and insulin sensitive index stimulated by insulin are higher in high fat group, a-linolenic acid group is the highest, saturated fatty acid group is the lowest, and the oleic acid group is medium; (2) The level of white fat > blood lipid , skeletal muscles TG -. the activity of fructose-1,6-bisphosphatase from liver are the highest in saturated fatty acids group, and the lowest in a -linolenic acid group; but the activity of pyruvate kinase > the level of glycogen in liver and skeletal muscles > the uncouple protein-1 mRNA level in brown fat ^ G1UT4 mRNA level in white fat and skeletal muscles are the highest in a -linolenic acid group, saturated fatty acid group is the lowest , and the oleic acid group is medium. Within the concentration of 0.125-1.OuM , a -linolenic acid can promote the PKB phosphorylation > the expression of GLUT4 protein and with dose-dependent > time-dependent relations, but the PKB does not haveabove relations; After adding PI3K inhibitor LY294002(15uM) in a -linolenic acid cultured skeletal muscle cells, there is no significant difference between a -linolenic acid group and control in the level of PKB phosphorylation and GLUT4 protein. (4) There is down-regulation on the PKB phosphorylation and GLUT4 protein expression with the palmitic acid and has a time-dependent relation; The effect of oleic acid on the PKB phosphorylation is not obvious, but on the down-regulation of GLUT4 protein is obvious and has a time-dependent relation. Conclusion: (1) All high-fat feeding with different fatty acids induce rat insulin resistance, but the degree of insulin resistance is the mildest in a -linolenic acid group within the high-feed group, this effect may be related with: a. a -linolenic acid can decline the level of TG in blood and skeletal muscles , which led to decrease the oxidation competition of the fatty acids and glucose oxidation; b. a -linolenic acid promote the expression of UCP-1 mRNA to enhance fat oxidation, reduce internal organs fats piling up; c. Advance the expression of GLUT4 mRNA in insulin sensitive tissue(skeletal muscles > fat), strengthen glucose transporting; d. improve the activity of PK and lower the activity of fructose-1,6-bisphosphatase from liver, enhance glycolysis and decline glyconeogenesis , promote glycogenesis . (2) within the suitable concentration, a -linolenic acid promote skeletal muscle PKB signal conduction by increasing PKB phosphorylation , improve the level of GLUT4 protein, which improve or avoid insulin resistance ,but the saturated fatty acid is opposite. This research imply that a -linolenic acid has energetic means for preventing and treating diabetes.