Abnormal arachidonate distribution in low-density lipoprotein and thoracic aorta in hyperinsulinemia.
The mechanism by which hyperinsulinemia promotes atherogenesis is unknown. The effects of hyperinsulinemia on risk factors for atherosclerosis were investigated by subcutaneously injecting rats daily with an insulin-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 increased urinary excretion of epinephrine and decreased urinary excretion of norepinephrine and dopamine, but had no significant effect on blood pressure or heart rate. Although insulin decreased plasma triglyceride 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 quality of the LDL particle. Insulin also increased the percentage of arachidonic acid (20:4) in LDL triglycerides by 37% (P < .05). In contrast, cholesteryl esters and triglycerides in the thoracic aorta were significantly increased (49% and 91%, respectively) by insulin treatment. Insulin increased the percentage of monounsaturated fatty acids and decreased the percentage of n-6 fatty acids, including arachidonate, in aortic triglycerides. Insulin also increased the percentage of palmitoleic acid (16:1) and decreased the percentages of saturated fatty acids and n-6 fatty acids in aortic cholesteryl esters. These results indicate that insulin induced deposition of cholesteryl esters and triglycerides, especially those containing monounsaturated fatty acids, and abnormal arachidonate distribution in LDL and tissues. The data further suggest that the development of atherosclerosis in response to hyperinsulinemia may be associated with arachidonate-rich triglycerides in LDL.
Okumura
K
K
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Kikuchi
M
M
Matsui
H
H
Naruse
K
K
Shimizu
K
K
Toki
Y
Y
Hashimoto
H
H
Ito
T
T
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014280:Triglycerides / Q000097:blood
D002788:Cholesterol Esters; D007328:Insulin; D008077:Lipoproteins, LDL; D010743:Phospholipids; D014280:Triglycerides; D016718:Arachidonic Acid; D002784:Cholesterol