Fluoxetine is a relatively novel class of selective serotonin reuptake inhibitors (SSRIs) with antidepressant properties. It seems to facilitate serotonergic transmission via down regulation of presynaptic inhibitory autoreceptors, with no effect on muscarinic receptors and doubtful effects on ? adrenergic receptors. Fluoxetine is mainly metabolized by cytochrome P450 (CYP) isoenzymes. It has been shown that CYP2C9、CYPD6, and CYP2C19 are major CYP isoforms responsible for the N demethylation of fluoxetine. Since both fluoxetine and its main metabolite norfluoxetine are the inhibitors of CYP2D6, CYP3A4, CYP2C9, and CYP2C19, there are some drug drug interactions of fluoxetine with other drugs for metabolism by those CYP isoenzymes, which results in interindividual differences in the pharmacokinetics and efficacy.

Genome-wide association studies ( CWAS) use high-throughout genotyping technologies to investigate the relation of hundreds of thousands of gene markers(genotype) with clinical conditions and measurable traits (phenotype). Type 2 diabetes mellitus results from the interaction of environmental factors with genetic variants. Many progresses have been acquired from GWAS. New gene regions have been discovered to be involved in the development and function of islet (3-cells, which provides new strategies for the etiology investigation, prevention, and treatment of type 2 diabetes mellitus.

Diabetic nephropathy is one of the most serious complications of diabetes mellitus and it seriously endangers people's health.Some previous studies indicate that the occurrence and development of diabetic nephropathy is not positively associated with control of blood glucose and course of disease,Its development has family aggregation and ethnic differences.In addition to environmental factors,genetic factors play an important role in the process of occurrence and development of diabetic nephropathy,Many genetic mutations can lead to a high degree of susceptibility to diabetic nephropathy.Discovery of some related genes of diabetic nephropathy and elucidation of these genes function provide an effective means in the early diagnosis,gene therapy and individualized drug therapy of diabetic nephropathy.In this review the action and function of discovered related genes of diabetic nephropathy are summarized.

The human ?3-adrenoceptor plays an important role in the regulation of energy mobilization and utilization. A missense mutation in codon 64 of the gene for the ?3-adrenoceptor with a replacement of tryptophan to arginine (Trp64Arg) was found. This polymorphism influences receptor function when expressed in artificial cell lines or in isolated human fat cells. It is associated with an earlier onset of type 2 diabetes mellitus, features of insulin resistance and tendency to gain weight. Recent evidences suggest that Trp64Arg has additive and interactive effects with a number of other candidate gene variants. The functional significance of human ?3-adrenoceptor polymorphism and its association with metabolic diseases are reviewed in this paper.

Objective To explore the distribution pattern of G protein-coupled receptor family C, group 6, subtype A (GPRC6A) mRNA in adult mice. Methods The distribution of GPRC6A mRNA in paraffin embedded adult mouse tissues was determined by highly sensitive nonradioactive cRNA probe in situ hybridization (ISH). We compared ISH with and without addition of tyramide signal amplification (TSA). GPRC6A wild-type and littermate GPRC6A null mice tissue sections were investigated by ISH. Results TSA greatly increased the sensitivity of ISH to detect GPRC6A mRNA in wild type mouse tissues. There was no detection of GPRC6A mRNA in GPRC6A gene specific knockout tissue in paraffin embedded tissue section. The mRNA of GPRC6A was detectable in the digestive gland or accessory digestive gland including salivary gland and pancreas, as well as in the tissues including kidney, testis, brain, muscle, and fat. Conclusion The mRNA distribution pattern of GPRC6A gene is compatible with the phenotype of GPRC6A knockout mice.

Aim ?3 adrenoceptor(?3-AR) is predominantly expressed in white and brown adipose tissue.?3 adrenoceptor agonist stimulates the lipolysis of white adipose tissue and non-shivering thermogenesis of brown adipose tissue to exert its antiobese action.Moreover,?3 adrenoceptor agonist increases the sensitivity and response of adipose tissue to insulin and it play an important role in the treatment of type 2 diabetes.In addition,?3 adrenoceptor agonist can also relax gastrointestinal spasm and show cardiovascular effect in human heart and vascular tissues.There has been increasing concerned in the study and development of ?3 AR agonists since 1983.Up to date,32 kinds of ?3 AR agonists have been identified.The development of ?3 AR agonists can provide new strategy and approach for pharmacotherapy of obesity and diabetic mellitus and will have Spaciously the used out look in the field of medicine.

Aim: Human ?_2-adrenoceptor contributes to the regulation of adipose tissue lipolysis,glucose homeostasis and vascular tension through endogenous catecholamines.This study was to investigate the association between polymorphisms of ?_2-adrenoceptor Arg16Gly and Gln27Glu and obesity in hypertensive patients.Methods Genotypes were determined using the PCR-RFLP and AS-PCR assay in 225 essential hypertensive patients and 125 healthy volunteers.Statistical analyses include one-way ANOVA and ?~2 analysis.Results The Arg16Gly and Gln27Glu polymorphisms were in Hardy-Weinberg equilibrium.The allele frequency of 27Glu in the patients with hypertension and obesity was 0.069 and significantly higher than that in the patients with hypertension and that in the healthy volunteers(P

The prevalent rates of overweight and obesity are steadily increasing all over the world. Previous studies of some candidate genes have indicated that most of the genes are associated with obesity in human adipose tissue. As much as 40% of the variations in body mass could be attributed to genetic difference. The β-adrenergic receptor (β-AR) plays a major role in the regulation of energy balance in humans. A high sympathetic nervous system activity has been shown to be associated with obesity and is believed to have pathogenetic relevance. Several common single nucleotide polymorphisms (SNPs) including Gly389Arg in β1-AR, Gln27Glu in β2-AR, and Trp64Arg in β3-AR in humans could alter receptor function and these variations ofβ-ARs were shown to have certain association with obesity. Here we summarize the genetic polymorphisms of human β-ARs and their potential impacts to obesity.

Aim To assess the protective role of chry-sophanol in rats with diabetes-associated cognitive de-cline (DACD) and explore the potential molecular mechanisms.Methods The learning and memory performance was assessed by Morris water maze test;the activities of AChE,ChAT,iNOS and oxidative stress markers including CAT,SOD and GSH-PX in the hippocampus were detected using respective com-mercial kits.The level of BDNF was also measured with commercial ELISA kit.Results Chrysophanol significantly improved learning and memory functions in the diabetic groups.Additionally,the activities of AChE,BDNF also found to be evidently increased, while decreased activities of ChAT,iNOS,CAT,SOD and GSH-PX were observed in the hippocampus of dia-betic rats.Conclusions Collectively,chrysophanol has a protective role against DACD and this neuropro-tection is associated with increasing BDNF level.Chry-sophanol can also suppress the activities of iNOS, CAT,SOD and GSH-PX in diabetic rats.It is likely to be a novel therapeutic drug for the treatment of diabetic patients with cognitive deficits in clinical practice.

Translation is a fundamental step in regulation of gene expression and abnormalities in this process may lead to cancer. In eukaryotic cells, translation of mRNA is mainly regulated by many eukaryotic initiation factors ( eIFs) . EIF3 plays an impor-tant role in translational regulation, cell growth and oncogenesis. The largest subunit of eIF3, eIF3a may play a role as a regulator of mRNAs. The relationship between eIF3a and oncogenesis has been found. Moreover, the eIF3a mRNA is ubiquitously ex-pressed in different cancer cells and can modulate the cell cycle. However, some studies indicate that eIF3a could provide protec-tion against evolution into higher malignancy and reduce the re-sistance to chemotherapy . The patients of high eIF3a expression could get a better prognosis . In fact, the role of eIF3a is still un-clear in cancer cells. EIF3a may be involved in the process of tumor pathophysiology, but its regulatory role is undulatory.