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1. In the present study, we investigated the associations of nicotinamide phosphoribosyltransferase (NAMPT)-3186 C/T and -948G/T polymorphisms with the risk of Type 2 diabetes mellitus (T2DM) and their impact on the efficacy of repaglinide in Chinese Han T2DM patients. 2. In all, 170 patients with T2DM and 129 healthy controls were genotyped for NAMPT-948G>T and -3186C>T polymorphisms. Thirty-five patients with different NAMPT -3186 C/T genotypes and the same organic anion-transporting polypeptide 1B1 (OATP1B1521) T/C genotype were randomly selected to undergo 8 weeks preprandial repaglinide treatment (1 mg, three times daily). Serum fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), glycated haemoglobin (HbAlc), fasting serum insulin (FINS), post-prandial serum insulin (PINS), triglyceride (TG), total cholesterol (CHO), homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were determined before and after repaglinide treatment. 3. After repaglinide treatment for 8 consecutive weeks, there were significantly decreases in PFG, PPG, HbAlc, CHO and LDL-C, and increases in FINS, HDL-C and the HDL-C : LDL-C ratio, in T2DM patients. The elevated PINS value in patients with CT genotypes was significantly lower than that in patients with the CC and TT genotypes (P T polymorphism is significantly associated with plasma levels of PINS and CHO in Chinese T2DM patients with repaglinide monotherapy.

This study showed that the polymorphisms KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) are associated with a heightened risk of developing type 2 diabetes mellitus (T2DM). We also explored the effects of these polymorphisms on the efficacy of repaglinide therapy in Chinese patients with T2DM. A total of 259 patients with T2DM and 188 healthy controls were genotyped. Forty patients with various genotypes were randomly selected to undergo an 8-week repaglinide treatment regimen. Patients with the G allele of the KCNJ11 Lys23Glu polymorphism showed higher levels of fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) (P < 0.05). After repaglinide treatment, patients with the GA or AA genotype showed higher levels of FPG, PPG, and glycated hemoglobin (HbA(1c)) compared with patients with the GG genotype (P < 0.05). Patients with the C allele of TCF7L2 rs290487(C/T) had higher total cholesterol levels and lower body mass index (BMI) (P < 0.05). In patients with the TT genotype, the drug showed better efficacy with respect to levels of fasting insulin, triglycerides, and low-density lipoprotein cholesterol (LDL-c) than in patients with the CC or CT genotype (P < 0.05). The KCNJ11 and TCF7L2 polymorphisms were associated with repaglinide efficacy.

To investigate the effect of nicotinamide mononucleotide (NMN) on insulin secretion and gene expressions of pancreatic and duodenal homeobox 1(PDX-1) and forkhead box-containing protein O-1 (FoxO1), which were important transcription factors for insulin secretion.Insulin secretion level in RIN-m5f cells was detected by rat insulin ELISA detection kit. The mRNA expression levels of PDX-1 and FoxO1 in RIN-m5f cells were analyzed by real-time PCR. The protein expression of PDX-1 was measured by Western blot.Insulin secretion levels in RIN-m5f cells treated with repaglinide (10 nmol/L) plus NMN (100 μmol/L) was significantly higher than those in the blank control, the DMSO control group, and the NMN (50 μmol/L) treated group (P0.05). The mRNA expression levels of PDX-1 in RIN-m5f cells treated with NMN (10, 50 and 100 μmol/L) for 36 h were significantly higher than those in the control group (P0.05, P0.01, and P0.001, respectively). There was marked differences in the mRNA expression levels of PDX-1 among different concentrations of NMN (P0.001), but no significant differences in the mRNA expression level of FoxO1 (P0.05). No significant difference was found in the protein expression levels of PDX-1 in RIN-m5f cells treated by NMN (50, 100, and 200 μmol/L) for 36 or 48 h compared with the control group (P0.05).NMN can stimulate insulin secretion and upregulate the mRNA expression of PDX-1 in RIN-m5f cells.

To explore the dose-dependent and time-dependent effect of docetaxel on the expression of mammalian eukaryotic initiation factor 3 subunit A (eIF3a) in lung cancer cell line.The human lung cancer cell line A549 was treated with gradient concentrations of docetaxel for different time. Real-time PCR and Western blot were used to detect mRNA and protein expression levels of eIF3a and alpha-tubulin, respectively.Docetaxel did not affect alpha-tubulin expression at either mRNA level or protein level. When A549 cells were treated with high concentration of docetaxel (30 μg/L), the expression level of eIF3a mRNA tended to increase in a time-dependent manner. Protein expression level of alpha-tubulin was not associated with eIF3a expression significantly in cells treated by docetaxel.Docetaxel could slightly increase the expression of eIF3a mRNA, and eIF3a does not regulate the expression of alpha-tubulin in A549 cells treated by docetaxel.