Markers of hyperglycemia in the vitreous humor. A systematic review and meta-analysis.

BACKGROUND: Vitreous humor has been extensively used in forensic practice to assess hyperglycemia after death. The results from different articles, for various hyperglycemia markers are highly variable, and a systematic analysis of the results from studies currently used in forensic practice as landmarks has not yet been performed. Therefore, we aimed to evaluate to usefulness and limits of using the values of vitreous glucose, lactic acid, beta-hydroxybutyrate, and 1,5 Anhydro-d-glucitol to detect postmortem hyperglycemia. MATERIALS AND METHODS: For this purpose, we performed a systematic review and a meta-analysis using the random-effects model to identify the threshold values and average differences for the markers mentioned above in the vitreous humor of diabetic versus nondiabetic subjects. RESULTS: We included eleven studies in the meta-analysis and found the following mean differences between the diabetic and nondiabetic groups: for glucose - 91.4 mg/dl, for lactate - 34.17 mg/dl, for the Traub formula - 111 mg/dl, for fructosamine - 0.71 mmol/L, for beta-hydroxybutyrate - 36.55 mg/dl and 1,5 Anhydro-d-glucitol - -15.2 mg/dl. We also gave practical recommendations, based on the range of values and 95% confidence intervals in normal subjects and controls to identify antemortem hyperglycemia and evaluated, whenever possible, threshold values for fatal diabetes. CONCLUSIONS: Glucose, Traub formula, fructosamine, and beta-hydroxy-butyrate can be used to detect postmortem hyperglycemia with some limitations; 1,5 Anhydro-d-glucitol can only be used to suggest the absence of a hyperglycemic status before death.

Quantification of 2-NBDG, a probe for glucose uptake, in GLUT1 overexpression in HEK293T cells by LC-MS/MS.

The growth and proliferation of most cancer cells involve the excessive uptake of glucose mediated by glucose transporters. An effective strategy for cancer therapy has been to inhibit the GLUTs that are usually overexpressed in a variety of tumor cells. 2-NBDG is a GLUT1 substrate that can be used as a probe for GLUT1 inhibitors. An accurate and simple assay for 2-NBDG in a HEK293T cell model overexpressing GLUT1 was developed using liquid chromatography-tandem mass spectrometry. Chromatographic separation was achieved using a Xbridge® Amide column (3.5 µm, 2.1 mm × 150 mm, Waters) with acetonitrile-water containing 2 µM ammonium acetate (80:20, v/v) at a flow rate of 0.25 mL/min. Mass detection was conducted in the parallel reaction monitoring (PRM) mode. The calibration curve for 2-NBDG showed good linearity in the concentration range of 5-500 ng/mL with satisfactory precision, a relative standard deviation ranging from 2.92 to 9.59% and accuracy with a relative error ranging from -13.14 to 7.34%. This method was successfully applied to quantify the uptake of GLUT1-mediated 2-NBDG, and the results clearly indicated inhibition of GLUT1 by WZB117 and quercetin (two potent glucose transporter inhibitors) in the GLUT1-HEK293T cell model. This study provides a convenient and accurate method for high-throughput screening of selective and promising GLUT1 inhibitors.

Association of time in range with hemoglobin A1c, glycated albumin and 1,5-anhydro-d-glucitol.

AIMS/INTRODUCTION: Hemoglobin A1c (HbA1c), glycated albumin (GA) and 1,5-anhydro-d-glucitol (1,5-AG) are used as indicators of glycemic control, whereas continuous glucose monitoring (CGM) is used to assess daily glucose profiles. The aim of this study was to investigate the relationships between CGM metrics, such as time in range (TIR), and glycemic control indicators. MATERIALS AND METHODS: We carried out retrospective CGM and blood tests on 189 outpatients with impaired glucose tolerance (n = 22), type 1 diabetes mellitus (n = 67) or type 2 diabetes mellitus (n = 100). RESULTS: In type 1 diabetes mellitus and type 2 diabetes mellitus patients, HbA1c and GA were negatively correlated with TIR, whereas 1,5-AG was positively correlated with TIR. In type 1 diabetes mellitus patients, a TIR of 70% corresponded to HbA1c, GA and 1,5-AG of 6.9% (95% confidence interval [CI] 6.5-7.2%), 20.3% (95% CI 19.0-21.7%) and 6.0 µg/mL (95% CI 5.1-6.9 µg/mL), respectively. In type 2 diabetes mellitus patients, a TIR of 70% corresponded to HbA1c, GA and 1,5-AG of 7.1% (95% CI 7.0-7.3%), 19.3% (95% CI 18.7-19.9%) and 10.0 µg/mL (95% CI 9.0-11.0 µg/mL), respectively. TIR values corresponding to HbA1c levels of 7.0% were 56.1% (95% CI 52.3-59.8%) and 74.2% (95% CI 71.3-77.2%) in type 1 diabetes mellitus and type 2 diabetes mellitus patients, respectively. CONCLUSIONS: The results of this study showed that the estimated HbA1c corresponding to a TIR of 70% was approximately 7.0% for both type 1 diabetes mellitus and type 2 diabetes mellitus patients, and that the estimated 1,5-AG calculated from the TIR of 70% might be different between type 1 diabetes mellitus and type 2 diabetes mellitus patients.

Association between 1,5-Anhydroglucitol and Acute C Peptide Response to Arginine among Patients with Type 2 Diabetes.

OBJECTIVE: The aim of this study was to explore the association of 1,5-anhydroglucitol with acute C peptide response (ACPR) to arginine among patients with type 2 diabetes. METHODS: Patients with type 2 diabetes were enrolled from the Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital. ACPR was assessed using arginine stimulation test. Decreased ß-cell function was defined as ACPR < 2.1. Multivariable logistic regression models were used to demonstrate the association between 1,5-anhydroglucitol and decreased ß-cell function. RESULTS: Finally, 623 patients with type 2 diabetes were enrolled into the analysis. Multivariable-adjusted odds ratios for decreased ß-cell function across quartiles of 1,5-anhydroglucitol were 1.00, 0.47 (95% confidence interval (CI) 0.23-0.99), 0.41 (95% CI 0.20-0.84), and 0.27 (95% CI 0.13-0.57) (P trend = 0.042), respectively. When 1,5-anhydroglucitol was considered as a continuous variable after logarithm, the corresponding odds ratio was 0.40 (95% CI 0.23-0.71). CONCLUSIONS: We demonstrated a dose-response linear association between 1,5-anhydroglucitol and ACPR. 1,5-Anhydroglucitol was likely to be associated with ß-cell function. Further analysis with large sample size and prospective study design is warranted to validate our findings.

Diabetes Screening: Detection and Application of Saliva 1,5-Anhydroglucitol by Liquid Chromatography-Mass Spectrometry.

CONTEXT: Unlike other commonly used invasive blood glucose-monitoring methods, saliva detection prevents patients from suffering physical uneasiness. However, there are few studies on saliva 1,5-anhydroglucitol (1,5-AG) in patients with diabetes mellitus (DM). OBJECTIVE: This study aimed to evaluate the effectiveness of saliva 1,5-AG in diabetes screening in a Chinese population. DESIGN AND PARTICIPANTS: This was a population-based cross-sectional study. A total of 641 subjects without a valid diabetic history were recruited from September 2018 to June 2019. Saliva 1,5-AG was measured with liquid chromatography-mass spectrometry. MAIN OUTCOME MEASURES: DM was defined per American Diabetes Association criteria. The efficiency of saliva 1,5-AG for diabetes screening was analyzed by receiver operating characteristic curves, and the optimal cutoff point was determined according to the Youden index. RESULTS: Saliva 1,5-AG levels in subjects with DM were lower than those in subjects who did not have DM (both P < .05). Saliva 1,5-AG was positively correlated with serum 1,5-AG and negatively correlated with blood glucose and glycated hemoglobin (HbA1c) (all P < .05). The optimal cutoff points of saliva 1,5-AG0 and 1,5-AG120 for diabetes screening were 0.436 µg/mL (sensitivity: 63.58%, specificity: 60.61%) and 0.438 µg/mL (sensitivity: 62.25%, specificity: 60.41%), respectively. Fasting plasma glucose (FPG) combined with fasting saliva 1,5-AG reduced the proportion of people who required an oral glucose tolerance test by 47.22% compared with FPG alone. CONCLUSION: Saliva 1,5-AG combined with FPG or HbA1c improved the efficiency of diabetes screening. Saliva 1,5-AG is robust in nonfasting measurements and a noninvasive and convenient tool for diabetes screening.

Formation and migration of α-dicarbonyl compounds during storage and reheating of a sugary food simulation system.

BACKGROUND: The thermal processing of food results in the formation of α-dicarbonyl compounds (α-DCs) such as glyoxal (GO), methylglyoxal (MGO), 2,3-butanedione (2,3-BD), and 3-deoxyglucosone (3-DG), which are precursors of potentially harmful advanced glycation end products. Some of the α-DCs found in food products might result from chemical deterioration reactions during storage and reheating. A range of sugary food simulation systems were stored at three different temperatures (4, 25, and 37 °C) and reheated using three different processing methods to investigate the formation and migration of α-DCs. RESULTS: During 20 days of storage, the concentration of α-DCs declined, following which the concentration remained approximately constant. Methylglyoxal was the major α-DC affected during storage, its relative content decreasing from 233.71 to 44.12 µg mL-1 in the glucose-lysine system. The concentration of α-DCs decreased with increasing temperature. Microwave reheating increased the formation of α-DC compounds. The largest increases in 3-DG concentrations were observed in the maltose-lysine systems (24.94 to 35.74 µg mL-1 ). The concentration of α-DCs only changed a little in response to reheating at 100 °C, but declined when reheated at 150 °C. CONCLUSION: The concentration of α-DCs following storage and reheating depends on the type of sugar, lysine content, temperature, and method of reheating. © 2020 Society of Chemical Industry.

1,5-Anhydroglucitol × glycated hemoglobin A1c/100 as a potential biomarker for islet ß-cell function among patients with type 2 diabetes.

AIMS: This study aimed to explore the level of and changes in the 1,5-anhydroglucitol × glycated hemoglobin A1c/100 (AH index, AHI) associated with different glucose metabolism statuses and to evaluate the islet function and insulin sensitivity of patients with type 2 diabetes (T2DM) with different AHI levels. METHODS: Of the 3562 subjects enrolled in this study, 1697 had T2DM. The disposition index (DI) was the product of islet secretion function and insulin sensitivity-related indexes. RESULTS: The mean AHI level was 1.0 (0.7-1.3) in the general population, while the mean AHI level in the T2DM group was 0.8 (0.5-1.2), which was significantly lower than that in the impaired glucose regulation and normal glucose tolerance group (both 1.2 (0.9-1.5), both P < 0.01). We further divided patients with T2DM into four subgroups according to the quartile of AHI. The results showed that with the increase in AHI level, the homeostasis model assessment of insulin resistance (HOMA-IR) decreased, while HOMA-ß, insulin generation index, insulin sensitivity index, and DI increased (all Pfor trend < 0.01). Multivariate logistic regression showed that the odds ratios for a low DI for increasing levels of AHI were 1.00, 0.22 (0.16-0.29), 0.16 (0.11-0.22), and 0.09 (0.06-0.13), showing a decreasing trend (Pfor trend < 0.05). CONCLUSION: The AHI could reflect the variation in glycemic disorder and the function of islet ß cells. The lower the AHI, the worse the glycemic disorder, as well as the islet ß-cell function.

Quantitation of α-Dicarbonyls and Advanced Glycation Endproducts in Conventional and Lactose-Hydrolyzed Ultrahigh Temperature Milk during 1 Year of Storage.

A comprehensive quantitative characterization of Maillard reaction products was carried out for conventional (CON) and lactose-hydrolyzed (LH) ultrahigh temperature (UHT) milk during storage at 20, 30, and 40 °C for 1 year. The accumulation of 3-deoxyglucosone (3-DG) and 3-deoxygalactosone (3-DGal) in LH-UHT milk ranged from 20-fold (at 20 °C) to 44-fold (at 40 °C) higher than that in CON-UHT milk. High temperature storage (40 °C) significantly accelerated the accumulation of 3-DG, 3-DGal, and 5-hydroxymethyl furfural but not the majority of the analyzed advanced glycation endproducts (AGEs). The concentrations of major AGEs including N-ε-carboxymethyllysine (CML), N-ε-carboxyethyllysine (CEL), methylglyoxal-hydroimidazolone isomers (MG-H1/H3), glyoxal-hydroimidazolone isomers (G-H1/H3), and G-H2 detected in CON milk during storage were in the range 12-700, 1-14, 8-45, 4-13, and 1-30 µM, respectively, while they were 30-570, 2-88, 17-150, 9-20, and 5-34 µM, respectively, in LH milk. Pyrraline, S-(carboxymethyl)cysteine (CMC), and glyoxal-lysine dimer were detected in lower levels, while MG-H2, methylglyoxal-lysine dimer, argpyrimidine, glyoxal-lysine-amide, glycolic acid-lysine-amide, and pentosidine were not detected in any of the milk samples. This work demonstrates for the first time that five of the analyzed AGEs (CML, CEL, MG-H1/H3, G-H1/H3, and G-H2) could be selected as markers for evaluation of the extent of the Maillard reaction in UHT milk. These results contribute to a better understanding of how Maillard reactions progress during storage of UHT milk and can be used to develop strategies to inhibit Maillard reactions in LH milk.

Measurement of α-dicarbonyl compounds in human saliva by pre-column derivatization HPLC.

Background α-Dicarbonyl compounds (α-DCs) have been detected in body fluids including plasma and urine and elevation of this sort of compounds in vivo has been associated with the development of many kinds of chronic diseases. However whether α-DCs are present in human saliva, and if their presence/absence can be related with various chronic diseases is yet to be determined. Methods In this study, a pre-column derivatization HPLC-UV method was developed to measure 3-deoxyglucosone (3-DG), glyoxal (GO), methylglyoxal (MGO), diacetyl (DA), and pentane-2,3-dione (PD) in human saliva employing 4-(2,3-dimethyl-6-quinoxalinyl)-1,2-benzenediamine (DQB) as a derivatizing reagent. The derivatization of the α-DCs is fast and the conditions are facile. The method was evaluated and the results show that it is suitable for the quantification of α-DCs in human saliva. Results In the measurements of these α-DCs in the saliva of 15 healthy subjects and 23 type 2 diabetes mellitus (T2DM) patients, we found that the concentrations of GO and MGO in the saliva of the diabetic patients were significantly higher than those in healthy subjects. As far as we know, this is the first time that salivary α-DC concentrations have been determined and associated with T2DM. Conclusions The developed method would be useful for the measurement of the salivary α-DC levels and the data acquired could be informative in the early screening for diabetes.

Mechanisms non-enzymatic browning in orange juice during storage.

The role of Reactive Carbonyl Species (RCS) derived from the Maillard reaction and ascorbic acid degradation on brown color formation was investigated in orange juice during storage. Eight RCS were monitored in aseptic juice over an 8-week period under refrigerated (4 °C) and accelerated conditions (35 °C). Significant changes in RCS concentrations were reported and positively correlated with color formation. Recombination experiments demonstrated the significant role of 3-deoxyglucosone and acetol on color formation as well as their interactions with glyoxal and methylglyoxal that lead to an increase in browning. Isotopic enrichment techniques further identified fructose as the main precursor of RCS, indicating the important role of Maillard reaction as a mechanism of non-enzymatic browning during orange juice storage. Finally, among the amino acids, tryptophan and glutamine showed the largest percentage losses in orange juice during storage and were reported to significantly impact the RCS composition and color formation.

Mitigation of 3-deoxyglucosone and 5-hydroxymethylfurfural in brown fermented milk via an alternative browning process based on the hydrolysis of endogenous lactose.

During the conventional production of brown fermented milk (BFM), unhealthy substances (3-deoxyglucosone (3-DG), methylglyoxal (MGO), and 5-hydroxymethylfurfural (HMF)) are generated during the Maillard browning step. Here, an alternative browning process based on the hydrolysis of endogenous lactose was established. Compared with the conventional process, 3-DG and HMF were decreased by 5.91 mg kg-1 and 0.39 mg kg-1 in the brown milk base under the alternative browning process, and thereafter, 3-DG and HMF were decreased by 54.5% and 65.0% in BFM. Investigation into the formation of 3-DG, MGO, and HMF in different chemical models showed that different sugars lead to different Maillard reaction products and browning rates, contributing to the mitigation of 3-DG and HMF. Apart from the mitigation of unhealthy Maillard compounds, hydrolyzing lactose and avoiding the addition of external glucose make the alternative browning process a theoretical and practical basis for improving the quality and safety of BFM.

Identification of [6-Hydroxy-2-(hydroxymethyl)-5-oxo-5,6-dihydro-2 H-pyran-3-yl]-cysteine (HHPC) as a Cysteine-specific Modification Formed from 3,4-Dideoxyglucosone-3-ene (3,4-DGE).

Glucose degradation products (GDPs) are formed from glucose and other reducing sugars during heat treatment, for example, in heat-sterilized peritoneal dialysis fluids or foods. Because of their reactive mono- and dicarbonyl structure, they react readily with proteins, resulting in the formation of advanced glycation end products (AGEs), loss of protein functionality, and cytotoxicity. Among the GDPs, 3,4-dideoxyglucosone-3-ene (3,4-DGE) exerts the strongest effects despite its relatively low concentration levels. The goal of the present study was therefore to identify the structure of specific protein modifications deriving from 3,4-DGE. A nonapeptide containing the reactive amino acids lysine, arginine, and cysteine was incubated with 3,4-DGE and the dominant GDPs 3-deoxyglucosone (3-DG) and 3-deoxygalactosone (3-DGal) in concentrations as present in peritoneal dialysis fluids (235 µM 3-DG, 100 µM 3-Gal, and 11 µM 3,4-DGE). Glycation rate and product formation were determined by ultra-HPLC-MS/MS (UHPLC-MS/MS). 3,4-DGE showed the strongest glycation activity. After 2 h of incubation, 3,4-DGE had modified 57% of the nonapeptide, whereas 3-DG had modified only 2% and 3-DGal had modified 29% of the peptide. A stable 3,4-DGE-derived cysteine modification was isolated. Its structure was determined by comprehensive NMR and MS experiments to be [6-hydroxy-2-(hydroxymethyl)-5-oxo-5,6-dihydro-2 H-pyran-3-yl]-cysteine (HHPC), which represents a novel cysteine-AGE derived from 3,4-DGE. The results indicate that 3,4-DGE might contribute to a severe loss of protein functionality by forming cysteine-specific AGEs, such as HHPC.

Aromatic aldehydes as selective fluorogenic derivatizing agents for α-dicarbonyl compounds. Application to HPLC analysis of some advanced glycation end products and oxidative stress biomarkers in human serum.

α-Dicarbonyl compounds (α-DCs) are very clinically important as they are considered as advanced glycation end products (AGEs) precursors and biomarkers for many chronic diseases such as diabetes and vascular diseases, in addition to their major role in progression of complications of such diseases. Aromatic aldehydes and ammonium acetate were productively used as a one-pot co-reagents for fluorogenic derivatization of α-DCs yielding fluorescent imidazole derivatives. Among the tried aromatic aldehydes, 4-carbomethoxybenzaldehyde yielded the products with best fluorescent characters. This approach for fluorogenic derivatization of α-DCs overcome the selectivity problem of the most commonly used derivatization reagent for α-DCs, α-diamino compounds, that can react unselectively with α-DCs and aldehydes. Separation of the formed imidazole derivatives of five α-DCs including glucosone, 3-deoxyglucosone, glyoxal, methyl glyoxal and dimethyl glyoxal together with ethylmethylglyoxal as an internal standard was carried out on an octyl column using a mobile phase consisted of methanol-water (15:85, v/v%) containing 0.2% formic acid with time programed flow, followed by fluorescence detection at excitation/emission wavelengths of 310/410 nm. The method showed excellent sensitivity for the targeted α-DCs with limits of detections ranging from 0.4 to 5.0 nM in human serum. Simple protein precipitation procedure was used for human serum treatment yielding very good recovery (91-105%) for the targeted α-DCs. The developed method was fully validated, then applied to the analysis of the five above mentioned clinically important α-DCs in serum samples of healthy, diabetic, rheumatic and cardiac disorders human volunteers. Due to the excellent analytical features of the developed method, including high selectivity and sensitivity, it was able to detect the pattern of the targeted α-DCs serum levels under the investigated different clinical conditions.

Metabolome analysis for pancreatic cancer risk in nested case-control study: Japan Public Health Center-based prospective Study.

Discovery of a high-risk group for pancreatic cancer is important for prevention of pancreatic cancer. The present study was conducted as a nested case-control study including 170 pancreatic cancer cases and 340 matched controls of our population-based cohort study involving 30 239 subjects who answered a baseline questionnaire and supplied blood samples. Twelve targeted metabolites were quantitatively analyzed by gas chromatography/tandem mass spectrometry. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were calculated using conditional logistic regression models. Statistically significant P-value was defined as P < .05. Increasing 1,5-anhydro-d-glucitol (1,5-AG) levels were associated with a decreasing trend in pancreatic cancer risk (OR of quartile 4 [Q4], 0.50; 95% CI, 0.27-0.93; P = .02). Increasing methionine levels were also associated with an increasing trend of pancreatic cancer risk (OR of Q4, 1.79; 95% CI, 0.94-3.40: P = .03). Additional adjustment for potential confounders attenuated the observed associations of 1,5-AG and methionine (P for trend = .06 and .07, respectively). Comparing subjects diagnosed in the first 0-6 years, higher levels of 1,5-AG, asparagine, tyrosine and uric acid showed a decreasing trend for pancreatic cancer risk (P for trend = .04, .04, .04 and .02, respectively), even after adjustment for potential confounders. We found that the 12 target metabolites were not associated with pancreatic cancer risk. However, metabolic changes in the subjects diagnosed in the first 0-6 years showed a similar tendency to our previous reports. These results might suggest that these metabolites are useful for early detection but not for prediction of pancreatic cancer.

Chemical exchange-sensitive spin-lock (CESL) MRI of glucose and analogs in brain tumors.

PURPOSE: Glucose uptake and metabolism can be measured by chemical exchange-sensitive spin-lock (CESL) MRI with an administration of glucose or its analogs. This study investigates the sensitivity, the spatiotemporal characteristics, and the signal source of glucoCESL with a 9L rat brain tumor model. METHODS: Dynamic CESL MRI with intravenous injection of D-glucose, 2-deoxy-D-glucose (2DG), and L-glucose were measured and compared with gadolinium-based dynamic contrast-enhanced (DCE) MRI. RESULTS: The CESL signals with an injection of glucose or analogs have faster and larger changes in tumors than normal brain tissue. In tumors, the CESL signal with 2DG injection has larger and slower peak response than that with D-glucose due to the accumulation of 2DG and 2DG-6-phosphate in the intracellular compartment, whereas L-glucose, which cannot be transported intracellularly by glucose transporters, only induces a small change. The initial glucoCESL maps (< 4 minutes) are qualitatively similar to DCE maps, whereas later maps (> 4 minutes) show more widespread responses. The rise times of D-glucose-CESL and 2DG-CESL signals in the tumor are slower than that of DCE. Our data suggest that the initial CESL contrast primarily reflects a passive increase of glucose content in the extracellular space of tumors due to a higher vascular permeability, whereas the later period may have a significant contribution from the uptake/metabolism of glucose in the intracellular compartment. CONCLUSIONS: Our results demonstrate that glucoCESL MRI has both extracellular and intracellular contributions, and can be a useful tool for measurements of both vascular permeability and glucose uptake in tumors.

Liver Plays a Major Role in FGF-21 Mediated Glucose Homeostasis.

BACKGROUND/AIMS: The liver is a vital organ in vertebrates and has a wide range of functions, including glucose absorption, glycogen storage and glucose production. Fibroblast growth factor (FGF)-21 is a metabolic regulator that is primarily produced by the liver. In this paper, we studied the effect of FGF-21 on glucose metabolism in the liver. METHODS: The glucose uptake of cells was detected by 2-Deoxy-d-[3H] glucose; the synergy between insulin and FGF-21 was evaluated. The mRNA expression of GLUT1-4, G6Pase and PEPCK was detected by real-time PCR. Glycogen synthesis was examined by the anthrone method. Blood samples to monitor glucose in db/db diabetic mice were obtained by tail snip. Glucose metabolism in the liver and adipose tissues was observed by fluorescence microscopy. RESULTS: In this study, FGF-21 stimulated glucose uptake by liver cells in both a dose and time-dependent manner, and at the same time, FGF-21 specifically stimulated GLUT1 expression in the liver cells. Furthermore, FGF-21 demonstrated a synergistic effect with insulin on glucose absorption, which is in accordance with enhanced GLUT-1 and -4 expression. Treatment with FGF-21 increased glycogen storage in liver cells. Consistent with in vitro results, FGF-21 lowered the plasma glucose level and stimulated GLUT1 expression and glycogen synthesis in db/db diabetic mice. Simultaneously, FGF-21 inhibited the gene expression of G6Pase and PEPCK. CONCLUSION: Our results suggest that FGF-21 clears up plasma glucose by stimulating glucose absorption in the liver of diabetic animals and decreases glucose release from the liver by inhibiting gluconeogenesis. Overall, these data indicate that the liver is an important target organ of FGF-21 to regulate glucose metabolism.

Liquid Chromatographic Analysis of α-Dicarbonyls Using Girard-T Reagent Derivatives.

The measurement of α-dicarbonyls and other degradation products of sugars has become important in view of their toxicity. Although there are several methods used for their analysis, most require long reaction times to form UV absorbing or fluorescent derivatives and the nonpolar nature of commonly used derivatives necessitates relatively high concentrations of organic solvents for elution in reverse phase liquid chromatography. The present method describes the use of Girard-T reagent in a simple, one step derivatization of α-dicarbonyls and conjugated aldehydes and analysis using ion-pair reverse phase liquid chromatography. The limit of detection was in the range of 0.06-0.09 µM (4-12 ng/mL) for glyoxal, methylglyoxal, 3-deoxyglucosone and 5-hydroxymethylfurfural with good linear response and reproducibility using UV detection. The hydrazone derivatives were stable for several days in solution. The method was used to study degradation of several sugars and quantification of the target α-dicarbonyls and 5-hydroxymethylfurfural in several soft drinks.

Antioxidant Capacity, Phenolic Constituents and Toxicity of Hot Water Extract from Red Maple Buds.

The present study reports, for the first time, the results of the antioxidant capacity and the phenolic composition of a hot water extract from red maple buds (RMB), as well as its safety. In this regard and comparatively to antioxidant standards, this extract exhibits a significant antiradical capacity when tested by 2,2-diphenyl-1-picrylhydrazyl (DPPH· ) and anion superoxide trapping assays. High-resolution mass spectrometric and nuclear magnetic resonance analyses permitted to determine for the first time, in red maple species, cyanidin-3-O-glucoside, quercetin-3-O-galactoside, quercetin-3-O-arabinoside, and quercetin. Also, the quantification of individual phenolics by high-performance liquid chromatography method revealed that ginnalin A at 117.0 mg/g is the major compound of RMB hot water extract. Finally, using flow cytometry evaluation, the extract of RMB was determined to have no toxicity neither to cause significant modification of apoptosis process, up to concentration of 100 µg/ml, on human peripheral blood neutrophils. These results allow anticipating various fields of application of RMB water extract.

Maillard reaction and caramelization during hazelnut roasting: A multiresponse kinetic study.

A comprehensive kinetic model indicating the elementary steps of Maillard reaction and caramelization during hazelnut roasting was proposed based on a multi-response kinetic modeling approach. Changes in the concentrations of sucrose, fructose, glucose, amino acids, 3-deoxyglucosone, 1-deoxyglucosone, 3,4-dideoxyglucosone, glyoxal, methylglyoxal, dimethylglyoxal, and 5-hydroxymethylfurfural were examined in hazelnuts during roasting at 150, 160 and 170°C for 15, 30, 60, 90, and 120min. The results suggested that 1,2-enolization was important in the interconversion of glucose and fructose, 5-hydroxymethylfurfural formation mainly proceeded via fructofuranosyl cation dehydration rather than 3-deoxglucosone, glucose contributed more than fructose and fructofuranosyl cation to the early stage of the Maillard reaction. Methylglyoxal and dimethylglyoxal were mainly formed from 1-deoxyglucosone with high reaction rate constants while glyoxal formed through glucose degradation. α-Dicarbonyl compounds could have a role in the formation of melanoidins. The temperature dependence of the reactions was complicated and could not be explained by the Arrhenius equation.

Effect of hydroxytyrosol and olive leaf extract on 1,2-dicarbonyl compounds, hydroxymethylfurfural and advanced glycation endproducts in a biscuit model.

The antiglycative activity of hydroxytyrosol (HT) and olive leaf extract (OLE) was investigated in wheat-flour biscuits. Quercetin (QE) and gallic acid (GA) were used as reference of antiglycative activity of phenolic compounds. HT, OLE, QE and GA were added in the range of 0.25-0.75% (w/w). Samples were compared against a control recipe baked at 180°C/20min. HT biscuit was able to inhibit efficiently the formation of hydroxymethylfurfural (HMF) and 3-deoxyglucosone (3-DG), as well as reduced the formation of overall free fluorescent AGEs and pentosidine. The inhibition of the 3-DG and HMF formation was directly and significantly correlated under controlled baking conditions. However, samples formulated with OLE exerted similar antiglycative capacity against pentosidine and Nε-carboxyethyl-lysine, although the amount of HT in the biscuit was 100-fold lower than the biscuit formulated with HT. Methylglyoxal, 3-DG, and glyoxal were the predominant 1,2-dicarbonyl compounds after baking but only 3-DG was significantly reduced by HT.