The Effect Of Insulin Like Growth Factor 1 On Proliferation And Migration Of Endothelial Cells Exposed To High Glucose

Part ⅠThe study about the effect of IGF1 on proliferation and migration of endothelial cells exposed to high glucoseObjective: The dysfunction of vascular endothelial plays an important role in diabetic vascular complications. The risk of cardiovascular and peripheral vascular occlusion in diabetes mellitus was far higher than in non-diabetes. Clinical study found that hyperglycemia was associated with diabetic vascular disease, endothelial cell dysfunction may be secondary to the hyperglycemia. Insulin like growth factor 1(IGF1) is important in regulating the cell growth, differentiation and apoptosis. Fox O(Forkhead box O) is a subfamily of Forkhead transcription factors, plays an important role in the regulation of apoptosis, stress and glucose metabolism in mammalian cells. Fox O1 was higher expressed in endothelial cells. Recent studies proved that IGF1 has variety effects on metabolic and vascular protection, and could directly against endothelial dysfunction in many aspects.Currently reports on IGF1 pay more attention to the research on nerve injury, in blood vessel protection reported less, and the mechanism was not clear. Our study was designed to investigate the effect and the possible mechanism of IGF1 on proliferation of endothelial cells in high glucose environment and migration.Methods: Human umbilical vein endothelial cells were cultured in vitro(HUVEC). The morphology of HUVEC was investigated under inverted microscope. HUVEC in asian fusion state were used in the experiment after serum starvation for 24 hours. Cultured HUVEC were divided into 5 groups [control group(5mmol/L glucose), high glucose group(25mmol/L glucose), hypertonic group(20mmol/L mannitol+5mmol/L glucose), high glucose+IGF1group(25mmol/L Gs+80ng/m L IGF1), high glucose+IGF1+AZD5363 group(25mmol/LGs+80ng/ml IGF1+5μmol/L AZD5363)]. The proliferation was detected by methyl thiazolyl tetrazolium(MTT), the migration was detected by transwellchamber. The m RNA expressions of Serine/threonine kinase(Akt) and Fox O1 were detected by real-time Polymerase Chain Reaction(real-time PCR). The protein expressions of Fox O1/p-Fox O1 and Akt/p-Akt were detected by immunohistochemisty.Results: Compared with the control group, the rate of cell survival in high glucose group decreased significantly [(69.10±4.65)% vs 100%,t=6.48,P<0.01], the transitional was decreased significantly(16.0±2.3 vs 45.8±12.4,t=5.27,P<0.01), the m RNA expression of Fox O1 was increased significantly(6.00±0.65 vs 1.14±0.15,t=12.62,P<0.01), the protein expressions of Fox O1/p-Fox O1 and Akt/p-Akt were increased. Compared with high glucose group, the cell survival rate and migration rate in high glucose+IGF1 group was increased significantly, the m RNA expression of Fox O1 was decreased significantly(2.73±1.52 vs6.00±0.65,t=3.42,P<0.05), the protein expressions of Fox O1/p-Fox O1 and Akt/p-Akt were decreased. Compared with high glucose group, the cell survival rate and migration rate in high glucose+IGF1+AZD5363 group had no significant difference(P>0.05), the m RNA expression of Fox O1 was decreased significantly(2.97±1.04 vs 6.00±0.65,t=3.42,P<0.05), the protein expressions of Fox O1/p-Fox O1 had no significant difference(P>0.05). The m RNA expression of Akt in five groups had no significant difference(F=0.39, P>0.05).Conclusion: IGF1 can improve the proliferation and migration of endothelial cell in high glucose. The potential mechanism could be IGF1 can regulate the expression of Fox O1 by activating Akt.Part ⅡThe relationship between serum IGF1 and HDL-C in type 2 diabetes mellitusObjective: The lipid metabolism disorder and atherosclerosis in type 2 diabetes mellitus(T2DM) patients were high.It was important to investigate the effect of IGF1 on serum lipid in the T2 DM, and to understand of its relationship with atherosclerosis. The aim of our study was to investgate the relationship between IGF1 and serum lipid levels in T2 DM patients.Methods: Detecting the levels of serum IGF1, total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C),apolipoprotein A(Lp A) and apolipoprotein B(Lp B) in 492 T2 DM patients. The 498 participants were divided into 3 groups according to the twenty-fifth percent and the seventy-fifth percent: low IGF1 group(G1), intermediate in IGF1 group(G2) and high IGF1group(G3). And investigating the relationship between IGF1 and HDL-C.Results: Compared with G2 group, the levels of BMI and FINS in G1 group were increased,HDL-C was decreased significantly in G1 group(P<0.05). Compared with G2 group, the levels of HDL-C, 2h PBG, FINS, 2h PINS, WHR, Hb A1 c in G3 group were decreased significantly(P<0.05), the rate of coronary heart disease was significantly reduced(P<0.05).After adjustment for age and sex, the level of IGF1 was positively correlated with HDL-C,the level of IGF1 was negatively correlated with age, course, waist circumference, FINS,2h PINS and IR. The stepwise multivariate linear regression analysis found TG, TC, LDL-C,WHR, 2h PBG, IGF1 and sex wrer enter the regression equation after adjusting for age and sex. When IGF1 increased 2.02 ng/d L, the HDL-C increased 1.00 mg/d L.Conclusion: The levels of IGF1 in T2 DM have a positive effect on HDL-C independently.IGF1 could prevent the occurring of cardiovascular disease in patients with type 2 diabetesmellitus.