Metformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear1. Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome-wide association study (GWAS), consisting of 13,123 participants of different ancestries. The C allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (p=6.6×10−14) greater metformin-induced in haemoglobin A1c (HbA1c) in 10,577 participants of European ancestry. rs8192675 is the top cis expression quantitative trait locus (cis-eQTL) for SLC2A2 in 1,226 human liver samples, suggesting a key role for hepatic GLUT2 in regulation of metformin action. Among obese individuals, C-allele homozygotes at rs8192675 had a 0.33% (3.6 mmol/mol) greater absolute HbA1c reduction than T-allele homozygotes. This was about half the effect seen with the addition of a DPP-4 inhibitor, and equated to a dose difference of 550mg of metformin, suggesting rs8192675 as a potential biomarker for stratified medicine.

BackgroundCardio-metabolic syndrome (CMS) is a highly prevalent condition. There is an urgent need to identify effective and integrated multi-disciplinary approaches that can reduce risk factors for CMS.MethodsSixty-two patients with a history of CMS were randomized 1:1 into two groups: a standard information -only group (control), or a self-regulated lifestyle waist circumference (patient-centered cognitive behavioral therapy) intervention group. A pretest and posttest, controlled, experimental design was used. Outcomes were measured at the baseline (week 0) and at the end of intervention (week 12). Comparisons were drawn between groups and over time.ResultsThe mean (standard deviation) age of the subjects was 48.6 (5.8) years ranging from 32 to 63, and 56.9% of the participants were female. Both groups showed no significant differences in Demographic variables and the metabolic syndrome indicators at baseline. While the control group only showed modest improvement after 12 weeks, compared to baseline, the intervention group demonstrated significant improvement from baseline. This study controlled for patients’ demographics and baseline characteristics when assessing the effects of intervention. After adjusting for age, education and baseline level, the experimental group and the control group were statistically significant different in the following post-treatment outcomes: WC (F = 35.96, P < 0.001), TG (F = 18.93, P < 0.001), RSBP (F = 33.89, P < 0.001) and SF-36(F = 157.93, P < 0.001). The results showed patients’ age and education were not strong predictors of patients’ outcome (including WC, TG, RSBP and SF-36).ConclusionsLifestyle intervention on patient-centered cognitive behavioral therapy can improve the physical and mental health conditions among individuals reporting a history of cardio-metabolic syndrome, and possibly provided preliminary benefits for the treatment of CMS.Trial registrationChinese Clinical Trial Register #, ChiCTR15006148.

Fusarium head blight (FHB) is a devastating wheat disease worldwide. To decipher the genetic architecture of FHB resistance in Chinese germplasm, a Wheat Association Panel for Scab Research (WAPS) consisting of 240 leading Chinese wheat cultivars and elite lines was genotyped using the 90K single nucleotide polymorphism (SNP) arrays. The FHB response was evaluated in the field nurseries in Wuhan in Hubei Province over four consecutive years from 2014 to 2017. Five quantitative trait loci (QTL) were consistently identified on chromosome arms 1AS, 2DL, 5AS, 5AL, and 7DS using a mixed linear model (MLM), explaining 5.6, 10.3, 5.7, 5.4, and 5.6% of phenotypic variation, respectively. The QTL on 5AS, 5AL, and 7DS QTL are probably novel. The allelic frequency analysis indicated that cultivars from the Middle and Lower Yangtze River Valleys harbored more favorable alleles and were therefore more resistant than those from other regions. To facilitate in-house germplasm screening and markerassisted selection (MAS), SNP-derived PCR markers were developed for the QTL regions on 1AS, 5AS, and 5AL QTL. In addition to the above five QTL, the WAPS population had a very low frequency of Fhb1, confirming that the gene is not widely used in Chinese wheat breeding programs. The resistant lines and molecular markers developed in this study are resources and information for enhancing FHB resistance in breeding populations by marker-assisted recurrent selection and gene stacking.

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Oolong tea could decrease body fat content and reduce body weight through improving lipid metabolism. Chronic consumption of oolong tea may prevent against obesity.

Aim This study evaluates the effect of dapagliflozin, a SGLT2 inhibitor, on fluid/electrolyte balance and its effect on urea transporter-A1 (UT-A1), aquaporin-2 (AQP2) and Na-K-2Cl cotransporter (NKCC2) protein abundance in diabetic rats. Methods Diabetes mellitus was induced by injection of streptozotocin into the tail vein. Serum Na+, K+, Cl− concentration, urine Na+, K+, Cl− excretion, blood glucose, urine glucose excretion, urine volume, urine osmolality and urine urea excretion were analyzed after the administration of dapagliflozin. UT-A1, AQP2 and NKCC2 proteins were detected by western blot. Results Dapagliflozin treatment decreased blood glucose by 38% at day 7 and 47% at day 14 and increased the urinary glucose excretion rate compared with the untreated diabetic animals. Increased 24-h urine volume, decreased urine osmolality and hyponatremia, hypokalemia and hypochloremia observed in diabetic rats were attenuated by dapagliflozin treatment. Western analysis showed that UT-A1, AQP2 and NKCC2 proteins are up-regulated in DM rats over control rats; dapagliflozin treatment results in a further increase in IM tip UT-A1 protein abundance by 42% at day 7 and 46% at day 14, but it did not affect the DM-induced up-regulation of AQP2 and NKCC2 proteins. Conclusion Dapagliflozin treatment augmented the compensatory changes in medullary transport proteins in DM. These changes will tend to conserve solute and water even with persistent glycosuria. Therefore, diabetic rats treated with dapagliflozin have a mild osmotic diuresis compared to non-diabetic animals, but this does not result in an electrolyte disorder or significant volume depletion.

Two experiments were conducted to investigate the effects of exogenous catalase (CAT) in the diet of weaned piglets on growth performance, oxidative capacity, and hepatic apoptosis after challenge with lipopolysaccharide (LPS). In experiment 1, 72 weaned piglets [Duroc × Landrace × Yorkshire, 6.90 ± 0.01 kg body weight (BW), 21 d of age] were randomly assigned to be fed either a basal diet (CON group) or a basal diet supplemented with 2,000 mg/kg CAT (CAT group; dietary CAT activity, 120 U/kg) for 35 d. Blood samples were collected on day 21 and day 35. At the end of this experiment, 12 pigs were selected from each of the CON and CAT groups, and six pigs were injected with LPS (50 μg/kg BW), while the remaining six pigs were injected with an equal amount of sterile saline, resulting in a 2 × 2 factorial arrangement of treatments (experiment 2). Blood samples and rectal temperature data were collected 0 and 4 h after challenge, and liver samples were obtained after evisceration. The gain-to-feed ratio was higher (P &lt; 0.05) in piglets in the CAT group than in those in the CON group from day 1 to 35. Catalase and total superoxide dismutase (T-SOD) activities were higher (P &lt; 0.05), whereas malondialdehyde (MDA) concentrations were lower (P &lt; 0.05), in piglets in the CAT group than in those in the CON group at day 35. During challenge, rectal temperature and liver MDA and H2O2 concentrations increased significantly (P &lt; 0.05), whereas plasma CAT and glutathione peroxidase (GSH-Px) activities and liver CAT activity decreased markedly (P &lt; 0.05), in LPS-challenged piglets 4 h post-challenge. Increased CAT activity and decreased MDA concentration were observed in the plasma and liver of piglets in the CAT group 4 h post-challenge (P &lt; 0.05). Dietary CAT supplementation markedly suppressed the LPS-induced decrease in plasma GSH-Px activity and liver CAT activity to levels observed in the CON group (P &lt; 0.05) as well as significantly decreasing the concentration and mRNA expression of caspase-3 and caspase-9 (P &lt; 0.05). LPS-induced liver injury was also attenuated by dietary CAT supplementation, as demonstrated by a decrease in liver caspase-3 mRNA expression (P &lt; 0.05). Overall, dietary supplementation with 2,000 mg/kg exogenous CAT (dietary CAT activity, 120 U/kg) improves growth performance and has a beneficial effect on antioxidant capacity in weaned piglets; alleviates oxidative stress and reduces liver damage by suppressing hepatic apoptosis in LPS-challenged piglets.