DOCOSAHEXANOIC ACID (DHA) IMPROVED GLUCOSE AND LIPID-METABOLISM IN KK-A(Y) MICE WITH GENETIC NON-INSULIN-DEPENDENT DIABETES-MELLITUS (NIDDM)

The hypoglycemic and hypolipidemic effect of docosahexaenoic acid (DHA ; C22:6 omega-3) ethyl ester was examined in KK-A(y) mice and neonatal streptozotocin-induced diabetic (NSZ) which are respectively obese an d lean animal models of non-insulin-dependent diabetes mellitus (NIDDM ), and in ddY normal mice. Single administration of DHA (500 mg/kg bod y, weight) to KK-A(y) mice significantly reduced (p<0.05) the blood gl ucose levels (BG) (p<0.05) and plasma free fatty acid levels (FFA) (p< 0.05) at 10h after oral administration when compared with control grou p. DHA (500 mg/kg body weight)-treated NSZ and normal mice, however, s howed no change in these parameters. In addition, repeated administrat ion of DHA (100 mg/kg) to KK-A(y) mice significantly suppressed the in crement of BG (p<0.05) and plasma triglyceride levels (TG) (p<0.01), a nd significantly decreased FFA (p<0.05) at 30d compared with control g roup. DHA also significantly decreased the blood glucose at 60 and 120 min on insulin tolerance test (ITT). From these findings, it seems li kely that DHA exhibits its hypoglycemic effects by increasing insulin sensitivity. It is concluded that DHA would be useful for treatment of obese type NIDDM with insulin resistance.