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Synergistic proliferation induced by insulin and glycated serum albumin in rat vascular smooth muscle cells

He Rong, Qu Aijuan, Mao Jieming, Wang Xian, Sun Wei

Department of Cardiology, Peking University Third Hospital.Beijing 100083；China

Abstract

Hyperglycemia, advanced glycation end products (AGEs), hyperinsulinemia and dyslipidemia may play roles in the development of diabetes-associated atherosclerosis and post-angioplasty restenosis. Clinically, their effects seem to be synergic.However, few studies have focused on the synergistic action of these factors. In the present study, we investigated wheth er glycated serum albumin (GSA) has a synergistic effect with insulin on the proliferation of vascular smooth muscle cells (VSMCs). VSMCs were isolated from rat thoracic aortas and cultured in fetal bovine serum (FBS)-free medium for 24 h, then exposed to GSA, insulin or GSA + insulin for 48 h with or without pretreatment of mitogen-activated protein kinase (MAPK) inhibitors or the antioxidant N-acetylcysteine (NAC). Cell growth rate was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay or cell counting. The changes of phosphorylated-p38 MAPK and phosphorylated-C-Jun N-terminal kinase 1/2 (JNK1/2) were measured by Western blot analysis. The results showed that only p38 MAPK, but not JNK was activated by GSA and insulin co-incubation. VSMC proliferation was increased by insulin (10-1000 nmol/L) or GSA (10, 100 #mu#g/mL). Co-incubation of insulin (100 nmol/L) and GSA (100 #mu#g/mL) caused a more potent increase in VSMC proliferation than insulin or GSA incubation alone. P38 MAPK inhibitor, SB203580,as well as NAC, could inhibit the VSMC proliferation induced by co-incubation of GSA and insulin. The results show that insulin enhances GSA-induced VSMC proliferation, which may be mediated through a reactive oxygen species (ROS)-p38 MAPK pathway.The synergism of AGEs and insulin may play a detrimental role in the pathogenesis of diabetic atherosclerosis and post-angioplasty restenosis.

Key words: Diabetes;Insulin;advanced glycation end products;glycated serum albumin;vascular smooth muscle cells

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Citing This Article：

He Rong, Qu Aijuan, Mao Jieming, Wang Xian, Sun Wei. Synergistic proliferation induced by insulin and glycated serum albumin in rat vascular smooth muscle cells. Acta Physiol Sin 2007; 59 (1): 1-7 (in Chinese with English abstract).