ABSTRACT
Objective To observe the effect of oxidized low-density lipoproteins (Ox-LDL),15-Deoxy-△ 12,14-prostaglandin J2 ( 15d-PGJ2 ),leukotrienes B4 ( LTB4 ) on mRNA expressions of peroxisome proliferator activated receptor γ2 ( PPARγ2 ),receptor activator of NF-κB ligand (RANKL),alkaline phosphatase ( ALP),and osteoprotegerin(OPG) in osteoblastic cells of rats; and to investigate the influence of these PPARγ2 endogenous ligands on bone metabolism.Methods Rat osteoblastic cells were cultured in vitro for 24 h in medium with different PPARγ2 endogenous ligands at various concentrations ( the final concentrations of Ox-LDL were 0,12.5,25,50μg/ml; the final concentrations of 15 d-PGJ2 were 0,10,20,30 μmol/L; the final concentrations of LTB4 were 0,0.1,1.0,10 μ mol/L).RT-PCR was performed to determine the mRNA expressions of PPARγ2,RANKL,ALP,and OPG in osteoblastic cells.Results RT-PCR analysis showed that Ox-LDL,15d-PGJ2,and LTB4 all down-regulated the mRNA expressions of RANKL,ALP,and OPG,while up-regulated the mRNA expressions of PPARγ2 in osteoblastic cells in a dose-dependent manner.Significant differences were found in interclass comparisons( P＜0.05 or P＜ 0.01 ).Conclusions These findings suggest that Ox-LDL,15d-PGJ2,and LTB4 suppress the expressions of osteogenic genes through activating the transcription activity of PPARγ2,and this may be a plausible mechanism of senile osteoporosis.
ABSTRACT
Objective To investigate the additive effects of uncoupling protein 2(UCP2) gene 3′-untranslated region(3′-UTR) 45-base pair insertion/deletion( I/D) variation and peroxisome proliferator activated receptor( PPAR)γ2 gene Pro12Ala variation on type 2 diabetes(T2DM) in Chinese Han popula-tion.Methods The UCP2 gene 3′-UTR I/D variation and PPARγ2 gene Pro12Ala variation were exam-ined by polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) in 490 type 2 dia-betes subjects and in 585 control subjects .The additive effects of the two gene mutations were analyzed . Results ⑴The frequency of PPARγ2 gene Pro12Ala variation in type 2 diabetes was not significantly dif-ferent from that in control subjects.(χ2 =0.058, P =0.809).In T2DM group, A12 allele carriers had larger waist circumference than Pro12Pro genotype carriers;Glucose stimulated insulin secretion by oral glu-cose tolerance test (OGTT) was significantly lower in carriers of the Ala12Ala or Pro12Ala genotype com-pared with Pro12Pro genotype.( Z =2.222, P =0.026; Z =2.051, P =0.040; Z =2.079, P =0.038 ) .⑵There wasn't significant difference among 3 genotypes with 3′-UTR I/D variation in UCP2 gene (χ2 =2.311 , P =0.315 ) .In control group , Glucose stimulated insulin secretion by oral glucose tolerance test ( OGTT) was significantly higher in carriers of the I/D or I/I genotype compared with D/D genotype ( Z =1.997 , P =0.046 ) .⑶The genotype carriers with Pro/Ala +Del/Del were the greatest relation to T2DM (OR=1.22, 95%CI 1.078~1.386).Conclusion Though the UCP2 gene mutation alone or the PPARγ2 gene mutation alone is not associated with T 2DM, the possible additive effects of the two micro genes increase the occurring of T 2DM.
ABSTRACT
The aim of this investigation was to determine whether a PPARγ2 Pro12Ala polymorphism was associated with insulin resistance, β-cell function and hypertension in Chinese populations. 289 unrelated Chinese subjects first diagnosed Type 2 diabetes (HbAC1＜6.0) were investigated, including 132 hypertensive diabetic (HTD) subjects, 157 normotensive diabetic (NTD) subjects. Blood pressure and anthropometric measurements were collected from all participants, as well as several venous blood samples during oral glucose tolerance test (OGTT). Biochemical measurements (high-density lipoprotein (HDL) and low-density lipoprotein-cholesterol (LDL), triglycerides) and PPARγ2 Pro12Ala genotype were also determined. And insulin resistance and β-cells function was assessed by HOMA-IR and HOMA-β respectively. The frequency of subjects bearing the Pro12Ala was lower in the hypertension group (3.03 %) than in the non-hypertension group (5.7 %) (P＜0.05) after adjusted for age, BMI and gender. Hypertensive diabetic Pro12Ala subjects had lower fasting plasma glucose level (P=0. 0127), and better glucose tolerance 60 min after oral glucose (P=0. 0361). Moreover, plasma insulin concentrations at 60 min was lower than those without A variant (P = 0. 0275), and both hypertensive Ala/Pro in HOMA-β (P = 0. 0455) and AUC for insulin (P=0. 0473) were higher, and HOMA-IR was lower (P=0. 0375) as compared with hypertensive Pro/Pro subjects. No association was observed between Pro12Ala genotype and BMI, total cholesterol, HDL- cholesterol or triglycerides in either group. Our findings suggested that the Ala 12 allele of the PPARγ2 gene may improve insulin resistance and ameliorate β-cell function reserves in T2DM with hypertension, and protect patients from hypertension in T2DM. As an important thrifty gene, environment factors may exerts an effect of PPAR γ2 on glucose homeostasis and insulin resistance.