Anti-atherogenic effect of insulin in vivo.
Metabolic syndrome is a risk factor for atherosclerosis and restenosis. In metabolic syndrome, insulin resistance coexists with hyperinsulinemia and hyperlipidemia. Hyperlipidemia has growth-promoting effects, whereas insulin has both growth-promoting and growth-inhibitory effects on vascular smooth muscle cells in vitro. The objective of this study was to investigate the effects of hyperlipidemia and hyperinsulinemia on vascular cell growth in vivo after arterial injury. Rats fed a low-fat diet were treated with either subcutaneous blank (LFC) or insulin (LFI) implants. Rats fed a high-fat diet also received blank (HFC) or insulin (HFI) implants. After 3 days, rats received balloon carotid injury, and 14 days later they were sacrificed to measure neointimal area and proliferation. Hyperinsulinemia was present in LFI and HFI and hyperlipidemia was present in HFC and HFI. Neointimal area was higher in HFC (0.153 +/- 0.009 mm(2), p < 0.05) but lower in LFI (0.098 +/- 0.005, p < 0.01) than LFC (0.127 +/- 0.005). In HFI (0.142 +/- 0.008, p < 0.05) neointimal area was not different from HFC or LFC. In conclusion, insulin reduced neointimal growth, but the effect of insulin was diminished by the high-fat diet. Thus, our results demonstrate an anti-atherogenic effect of insulin in vivo and suggest that in metabolic syndrome insulin resistance rather than hyperinsulinemia is the atherogenic risk factor.
Kim
Tony
T
Department of Physiology, University of Toronto, Toronto, Canada.
Chan
Kalam K
KK
Dhaliwall
Jiwanjeet K
JK
Huynh
Nghia
N
Suen
Renee
R
Uchino
Hiroshi
H
Naigamwalla
Dinaz
D
Bendeck
Michelle P
MP
Giacca
Adria
A
D000818:Animals; D050197:Atherosclerosis / Q000517:prevention & control*; D002339:Carotid Arteries / Q000473:pathology; D020212:Carotid Artery Injuries / Q000150:complications / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D002404:Catheterization; D002455:Cell Division / Q000187:drug effects; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D006946:Hyperinsulinism / Q000150:complications; D006949:Hyperlipidemias / Q000150:complications; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D004041:Dietary Fats; D004343:Drug Implants; D007328:Insulin