ABNORMAL ARACHIDONATE DISTRIBUTION IN LOW-DENSITY-LIPOPROTEIN AND THORACIC AORTA IN HYPERINSULINEMIA

The mechanism by which hyperinsulinemia promotes atherogenesis is unkn own. The effects of hyperinsulinemia on risk factors for atheroscleros is were investigated by subcutaneously injecting rats daily with an in sulin-zinc suspension (20 U/kg) for 12 weeks. After this period, body mass and food consumption did not differ significantly between control and insulin-treated animals. Daily insulin injection significantly in creased urinary excretion of epinephrine and decreased urinary excreti on of norepinephrine and dopamine, but had no significant effect on bl ood pressure or heart rate, Although insulin decreased plasma triglyce ride concentration by 44% (P < .01), the triglyceride to protein ratio in plasma low-density lipoprotein (LDL) was increased by 34% (P < .05 ) in insulin-treated rats; the cholesterol to protein and triglyceride to protein ratios remained unaffected, indicating a change in the qua lity of the LDL particle. Insulin also increased the percentage of ara chidonic acid (20:4) in LDL triglycerides by 37% (P < .05). In contras t, cholesteryl esters and triglycerides in the thoracic aorta were sig nificantly increased (49% and 91%, respectively) by insulin treatment. Insulin increased the percentage of monounsaturated fatty acids and d ecreased the percentage of n-6 fatty acids, including arachidonate, in aortic triglycerides. Insulin also increased the percentage of palmit oleic acid (16:1) and decreased the percentages of saturated fatty aci ds and n-6 fatty acids in aortic cholesteryl esters. These results ind icate that insulin induced deposition of cholesteryl esters and trigly cerides, especially those containing monounsaturated fatty acids, and abnormal arachidonate distribution in LDL and tissues. The data furthe r suggest that the development of atherosclerosis in response to hyper insulinemia may be associated with arachidonate-rich triglycerides in LDL. Copyright (C) 1995 by W.B. Saunders Company