RESULTS: Targeted and non-targeted metabolomics for both polar and semi-polar metabolites of Phialemonium curvatum AWO2 (DSM 23903) cultivated in MSM with palm oil (MSM-P) or glucose (MSM-G) as carbon sources were obtained. Targeted metabolomics on central carbon metabolism of tricarboxylic acid (TCA) cycle and glyoxylate cycle were analysed using LC-MS/MS-TripleQ and GC-MS, while untargeted metabolite profiling was performed using LC-MS/MS-QTOF followed by multivariate analysis. Targeted metabolomics analysis showed that glyoxylate pathway and TCA cycle were recruited at central carbon metabolism for triglyceride and glucose catabolism, respectively. Significant differences in organic acids concentration of about 4- to 8-fold were observed for citric acid, succinic acid, malic acid, and oxaloacetic acid. Correlation of organic acids concentration and key enzymes involved in the central carbon metabolism was further determined by enzymatic assays. On the other hand, the untargeted profiling revealed seven metabolites undergoing significant changes between MSM-P and MSM-G cultures.
CONCLUSIONS: Overall, this study has provided insights on the understanding on the effect of triglycerides and sugar as carbon source in fungi global metabolic pathway, which might become important for future optimization of carbon flux engineering in fungi to improve organic acids production when vegetable oil is applied as the sole carbon source.
MATERIALS/METHODS: Twelve- to fourteen-week-old CAV-1 knockout (KO) and genetically matched wild-type (WT) male mice were randomized by genotype to one of two dietary regimens: ad libitum (ad lib) food intake or 40% CR for 4 weeks. Three weeks following the onset of dietary restriction, all groups were assessed for insulin sensitivity. At the end of the study, all groups were assessed for fasting glucose, insulin, HOMA-IR, lipids, corticosterone levels and blood pressure (BP). Aldosterone secretion was determined from acutely isolated Zona Glomerulosa cells.
RESULTS: We confirmed that the CAV-1 KO mice on the ad lib diet display a phenotype consistent with the cardiometabolic syndrome, as shown by higher systolic BP (SBP), plasma glucose, HOMA-IR and aldosterone levels despite lower body weight compared with WT mice on the ad lib diet. CAV-1 KO mice maintained their body weight on the ad lib diet, but had substantially greater weight loss with CR, as compared to caloric restricted WT mice. CR-mediated changes in weight were associated with dramatic improvements in glucose and insulin tolerance in both genotypes. These responses to CR, however, were more robust in CAV-1KO vs. WT mice and were accompanied by reductions in plasma glucose, insulin and HOMA-IR in CAV-1KO but not WT mice. Surprisingly, in the CAV-1 KO, but not in WT mice, CR was associated with increased SBP and aldosterone levels, suggesting that in CAV-1 KO mice CR induced an increase in some CV risk factors.
CONCLUSIONS: CR improved the metabolic phenotype in CAV-1 KO mice by increasing insulin sensitivity; nevertheless, this intervention also increased CV risk by inappropriate adaptive responses in the RAAS and BP.
STUDY DESIGN: A wide range of socio-demographic characteristics of Chinese, Malay and Indian women attending routine gynecologic care in Singapore were prospectively collected. Physical performance was objectively measured by hand grip strength and the Short Physical Performance Battery. Percent VAT was determined by dual-energy X-ray absorptiometry. Fasting serum concentrations of glucose, insulin, IL-6, TNF- α, and hs-CRP were measured.
MAIN OUTCOME MEASURE: was insulin resistance, expressed as the homeostatic model assessment of insulin resistance (HOMA-IR).
RESULTS: 1159 women were analyzed, mean age 56.3 (range 45-69) years, comprising women of Chinese (84.0%), Indian (10.2%), and Malay (5.7%) ethnic origins. The adjusted mean differences for obesity (0.66, 95% CI 0.32-1.00), VAT area in the highest vs lowest tertile (1.03, 95% CI 0.73-1.34), low physical performance (0.63, 95% CI 0.05-1.24), and highest vs lowest tertile of TNF- α (0.35, 95% CI 0.13-0.57) were independently associated with HOMA-IR. Women of Malay and Indian ethnicity had higher crude HOMA-IR than Chinese women. However, after adjustment for obesity, VAT, physical performance, and TNF- α, no differences in mean HOMA-IR remained, when comparing Chinese women with those of Malay ethnicity (0.27, 95% CI -0.12 to 0.66) and with those of Indian ethnicity (0.30, 95% CI -0.01 to 0.66).
CONCLUSIONS: Insulin resistance was independently associated with obesity, high VAT, low physical performance, and high levels of TNF- α in midlife Singaporean women. These variables entirely explained the significant differences in insulin resistance between women of Chinese, Malay and Indian ethnicity.
PURPOSE: The present work aimed to assess the antidiabetic potential of arjunolic acid (AA) isolated from Terminalia arjuna in type 2 diabetic rats.
STUDY DESIGN: After extraction, isolation and purification, AA was orally administered to type 2 diabetic Sprague Dawley rats to investigate antidiabetic effect of AA.
METHOD: T2DM was induced via single intraperitoneal injection of streptozotocin-nicotinamide (STZ-NIC) in adult male rats. After 10 days, fasting and random blood glucose (FBG and RBG), body weight (BW), food and water intake, serum C-peptide, insulin and glycated hemoglobin (HbA1c) was measured to confirm T2DM development. Dose dependent effects of orally administered AA (25 and 50 mg/kg/day) for 4 weeks was investigated by measuring BW variation, fasting and postprandial hyperglycemia, oral glucose tolerance test (OGTT), and levels of serum HbA1c, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), serum and pancreatic C-peptide, insulin, growth differentiation factor 15 (GDF-15), serum and pancreatic inflammatory cytokines.
RESULTS: The oral administration of AA in preclinical model of T2DM significantly normalized FBG and RBG, restored BW, controlled polyphagia, polydipsia and glucose tolerance. In addition, AA notably reduced serum HbA1c, TC, TG, LDL with non-significant increase in HDL. On the other hand, significant increase in serum and pancreatic C-peptide and insulin was observed with AA treatment, while serum and pancreatic GDF-15 were non-significantly altered in AA treated diabetic rats. Moreover, AA showed dose dependent reduction in serum and pancreatic proinflammatory cytokines including TNF-α, IL-1β and IL-6.
CONCLUSION: For the first time our findings highlighted AA as a potential candidate in type 2 diabetic conditions.
METHODS: PLHIV from a regional observational cohort without DM prior to antiretroviral therapy (ART) initiation were included in the analysis. DM was defined as having a fasting blood glucose ≥126 mg/dL, glycated haemoglobin ≥6.5%, a two-hour plasma glucose ≥200 mg/dL, or a random plasma glucose ≥200 mg/dL. A Cox regression model, stratified by site, was used to identify risk factors associated with DM.
RESULTS AND DISCUSSION: Of the 1927 participants included, 127 were diagnosed with DM after ART initiation. Median follow-up time from ART initiation to DM diagnosis was 5.9 years (interquartile range (IQR): 2.8 to 8.9 years). The crude incidence rate of DM was 1.08 per 100 person-years (100 PYS), 95% confidence interval (CI) (0.9 to 1.3). In the multivariate analysis, later years of follow-up (2011 to 2013: HR = 2.34, 95% CI 1.14 to 4.79, p = 0.02; and 2014 to 2017: HR = 7.20, 95% CI 3.27 to 15.87, p 50 years: HR = 4.19, 95% CI 2.12 to 8.28, p 30 kg/m2 (HR = 4.3, 95% CI 1.53 to 12.09, p = 0.006) compared to BMI <18.5 kg/m2 , and high blood pressure (HR = 2.05, 95% CI 1.16 to 3.63, p = 0.013) compared to those without high blood pressure, were associated with developing DM. The hazard was reduced for females (HR = 0.47, 95% CI 0.28 to 0.80, p = 0.006).
CONCLUSIONS: Type 2 DM in HIV-infected Asians was associated with later years of follow-up, high blood pressure, obesity and older age. This highlights the importance of monitoring and routine screening for non-communicable diseases including DM as PLHIV age.
METHODS: Geraniin (95% purity) was extracted and purified from rambutan rind. Two groups of male Sprague-Dawley rats were fed with 60% high-fat diet and standard rat chow, respectively, for 12 weeks. High-fat diet-treated rats were then administered geraniin at different doses. Body weight, blood pressure and blood glucose readings were measured. At the end of treatment, blood was collected for analysis of glycated haemoglobin A1c (HbA1c), insulin, advanced glycation end-product (AGE) levels, renin, aldosterone and electrolytes.
RESULTS: Within the first week of treatment, even the lowest dose of geraniin caused a significant reduction in blood pressure, which was comparable to control diet-treated rats. There were no changes in serum electrolytes, renin or aldosterone. Similarly, there was a significant reduction in serum insulin, insulin resistance and AGE levels at the lowest dose. However, there was no significant decrease in fasting blood glucose or HbA1c. The effects of decreasing insulin, insulin resistance and AGEs were observed only at the lower doses, unlike the results observed for blood pressure reduction.
CONCLUSION: Geraniin at lower doses improved blood pressure and other metabolic parameters. Secondary metabolites of geraniin, associated with antihypertensive activity, are relatively different to those involved in inhibiting AGE formation and increasing insulin sensitivity. The secondary metabolites of geraniin may be individually responsible for the bioactivities demonstrated.