Association of β3 Adrenergic Receptor and Peroxisome Proliferator-activated Receptor Gamma 2 Polymorphisms With Insulin Sensitivity:A Twin Study

Objective To study the effect of β3 adrenergic receptor （β3AR） Trp64Arg and peroxisome proliferator activated receptor gamma 2 （PPAR72） Prol2Ala polymorphisms on insulin resistance. Methods One hundred and eight dizygotic twin pairs were enrolled in this study. Microsatellite polymorphism was used to diagnose zygosity of twins. Insulin sensitivity was estimated with logarithm transformed homeostasis model assessment （HOMA）. PCR-RFLP analysis was performed to detect the variants. As a supplement to the sib-pair method, identity by state （IBS） was used to analyze the association of polymorphisms with insulin sensitivity. Results The genotype frequencies of Trp64Trg, Trp64Arg, and Arg64Arg were 72.3%, 23.8%, and 3.9%, respectively, while the genotype frequencies of Pro12Pro, Pro12Ala, and Ala12Ala were 89.9%, 9.6%, and 0.5%, respectively. For β3AR Trp64Arg the interclass co-twin correlations of Waist-to-hip ratio （WHR）, blood glucose （GLU）, and insulin （INS）, homeostasis model assessment insulin resistance index （HOMA-IR） of the twin pairs sharing 2 alleles of IBS were greater than those sharing 0-1 allele of IBS, and HOMA4R had statistic significance. For PPAR3t2 Prol2Ala most traits of twin pairs sharing 2 alleles of IBS had greater correlations and statistic significance in body mass index （BMI）, WHR, percent of body fat （PBF） and GLU, but there were low correlations of either insulin or HOMA-IR of twin pairs sharing 1 or 2 alleles of IBS. The combined effects of the two variations showed less squared significant twin-pair differences of INS and HOMA-IR among twins sharing 4 alleles of IBS. Condusions β3AR Trp64Arg and PPAR）,2 Pro 12Ala polymorphisms might be associated with insulin resistance and obesity, and there might be slight synergistic effects between this two gene loci, and further studies are necessary to confirm this finding.

Jueming Prescription(决明方) Reduces Body Weight by Increasing the mRNA Expressions of Beta3-Adrenergic Receptor and Uncoupling Protein-2 in Adipose Tissue of Diet-Induced Obese Rats

Objective： To investigate the antiobesity effect of Jueming Prescription （决明方, JMP）, a Chinese herbal medicine formula, and its influence on mRNA expressions of beta3 adrenergic receptor （beta3-AR） and uncoupling protein-2 （UCP-2） in adipose tissue of diet-induced obese rats. Methods： Fifty male Sprague-Dawley rats were randomly divided into the normal control group （n=8） that was on a standard chow diet, and the obese model group （n=42） that was on a diet of high fat chow. Two weeks after the high fat diet, 29 obese rats in the obese model group were further randomly divided into 3 groups： the untreated obese model group （n=9）, the met＇formin group （n=10, mefformin 300 mg-kg-1.day-1）, and the JMP group （n=10, JMP 4 g.kg-1.dayl）. After 8-week treatment, body weight, wet weight of visceral fat, and percentage of body fat （PBF） were measured. The levels of fasting blood glucose, serum lipids, and insulin were assessed, and insulin sensitivity index （ISI） was calculated. The adipose tissue section was stained with hematoxylin-Eosin, and the cellular diameter and quantity of adipocytes were evaluated by light microscopy. The mRNA expressions of beta3-AR and UCP-2 from the pet-renal fat tissue were determined by real-time reverse transcription polymerase chain reaction （RT-PCR）. Results： Compared with the obese model group, treatment with JMP resulted in significantly lower body weight, wet weight of visceral fat, PBF, and diameter of adipocytes, and significantly higher level of high-density lipoprotein cholesterol, ISI （all P〈0.01）, JMP increased the mRNA expressions of beta3-AR and UCP-2 from pedrenal fat tissue （P〈0.05, P〈0.01）. Conclusions： JMP could reduce body weight and adipocyte size; and the effect was associated with the up-regulation of beta3-AR and UCP-2 expressions in the adipose tissue and improvement of insulin sensitivity.

Association of GYS1 and β_3-AR gene with postprandial hyperglycemia and serum uric acid in type 2 diabetes mellitus

Objective To determine the relationships of Met416Val and XbaI polymorphism of muscle glycogen synthase (GYS1) gene and Trg64Arg variant of the β 3 adrenergic receptor (β 3 AR) gene with type 2 diabetes mellitus (DM) and its intermediate phenotypes in the Chinese population Methods Polymerase chain reaction oligonucleotide ligation assay and restriction fragment length polymorphism assay were used to evaluate the GYS1 and β 3 AR gene polymorphisms in 102 pairs of case control Chinese spouses Results Subjects with Met416Val variant had a significantly higher 2 hour post glucose level than subjects without this variant had in diabetic group ( P =0 032) The Met416Val polymorphism of GYS1 gene was not significantly associated with the risk of type 2 DM (adjusted OR=1 67; 95% CI: 0 73-3 81, P =0 223) Subjects with Trp64Arg variant had a significantly higher serum uric acid level than subjects without this variant had in diabetic group ( P =0 034) The combination of BMI and Arg64 allele carrier of the β 3 AR gene increased the diabetic risk over four fold (adjusted OR=4 00; 95%CI: 1 53-10 45, P =0 005) Conclusions In the Chinese population, Met416Val polymorphism is identified in a subgroup of diabetic subjects with high 2 hour post glucose It will explain why some diabetic patients appear to be genetically predisposed to developing high postpradial glucose level The presence of the Arg64 allele in the β 3 AR gene may predispose patients to higher serum uric acid level