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1.
Double transcranial direct current stimulation of the brain increases cerebral energy levels and systemic glucose tolerance in men.
Wardzinski, EK, Friedrichsen, L, Dannenberger, S, Kistenmacher, A, Melchert, UH, Jauch-Chara, K, Oltmanns, KM
Journal of neuroendocrinology. 2019;(4):e12688
Abstract
Transcranial direct current stimulation (tDCS) is a neuromodulatory method that has been tested experimentally and has already been used as an adjuvant therapeutic option to treat a number of neurological disorders and neuropsychiatric diseases. Beyond its well known local effects within the brain, tDCS also transiently promotes systemic glucose uptake and reduces the activity of the neurohormonal stress axes. We aimed to test whether the effects of a single tDCS application could be replicated upon double stimulation to persistently improve systemic glucose tolerance and stress axes activity in humans. In a single-blinded cross-over study, we examined 15 healthy male volunteers. Anodal tDCS vs sham was applied twice in series. Systemic glucose tolerance was investigated by the standard hyperinsulinaemic-euglycaemic glucose clamp procedure, and parameters of neurohormonal stress axes activity were measured. Because tDCS-induced brain energy consumption has been shown to be part of the mechanism underlying the assumed effects, we monitored the cerebral high-energy phosphates ATP and phosphocreatine by 31 phosphorus magnetic resonance spectroscopy. As hypothesised, analyses revealed that double anodal tDCS persistently increases glucose tolerance compared to sham. Moreover, we observed a significant rise in cerebral high-energy phosphate content upon double tDCS. Accordingly, the activity of the neurohormonal stress axes was reduced upon tDCS compared to sham. Our data demonstrate that double tDCS promotes systemic glucose uptake and reduces stress axes activity in healthy humans. These effects suggest that repetitive tDCS may be a future non-pharmacological option for combating glucose intolerance in type 2 diabetes patients.
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2.
Elevated Prevalence of Abnormal Glucose Metabolism and Other Endocrine Disorders in Patients with β-Thalassemia Major: A Meta-Analysis.
He, LN, Chen, W, Yang, Y, Xie, YJ, Xiong, ZY, Chen, DY, Lu, D, Liu, NQ, Yang, YH, Sun, XF
BioMed research international. 2019;:6573497
Abstract
BACKGROUND Endocrinopathies are common in patients with β-thalassemia major despite parenteral iron chelation therapy with deferoxamine. Prevalence of abnormal glucose metabolism in previous studies was controversial. The aim of this study was to discuss the prevalence of abnormal glucose metabolism in β-thalassemia major based on a meta-analysis. METHODS PubMed, ScienceDirect, Springerlink, Ovid, Web of Science, MEDLINE, Wanfang database, and Chinese National Knowledge Internet were searched for relevant articles. Two authors selected the articles according to the inclusion criteria and then extracted the data. The prevalence of diabetes mellitus (DM) in β-thalassemia major was defined as the primary outcome. The prevalence with the 95% confidence interval (95%CI) was used to evaluate the proportion of abnormal glucose metabolism and other endocrine disorders in patients with β-thalassemia major. Subgroup analyses were applied to explore the prevalence in different regions. Sensitivity analysis and publication bias assessment were also conducted. RESULTS A total of 44 studies with 16605 cases were included in this analysis. Diabetes mellitus was present in 6.54% (95% CI: 5.30%-7.78%). The fixed subgroup study revealed that the region with the highest prevalence was the Middle East (prevalence= 7.90%, 95% CI: 5.75%-10.05%). The accumulated meta-analysis revealed that the prevalence of DM in β-thalassemia major was relatively steady in each year. The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and other endocrine disorders in β-thalassemia major was 17.21% (95% CI: 8.43%-26.00%), 12.46% (95% CI: 5.98%-18.94%), and 43.92% (95% CI: 37.94%-49.89%), respectively. Sensitivity analysis showed that the pooled results were robust; publication bias assessment revealed that there was no significant evidence that the pooled results were influenced by publication bias. CONCLUSION High prevalence of endocrine disorders involving abnormal glucose metabolism was detected in β-thalassemia major. Treatment and prevention measurements may be necessary to prevent growth and endocrine problems.
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3.
Potato product form impacts in vitro starch digestibility and glucose transport but only modestly impacts 24 h blood glucose response in humans.
Li, M, George, J, Hunter, S, Hamaker, B, Mattes, R, Ferruzzi, MG
Food & function. 2019;(4):1846-1855
Abstract
Potatoes are rich in phenolic compounds which have been reported to impact starch digestion and intestinal glucose transport in model systems through phenolic-starch interactions. While these effects are well documented for pigmented potatoes and in model systems, the relevance of phenolics to the glycemic properties of processed colorless potato-based foods under naturalistic conditions remains unclear. This study assessed impacts of processing on phenolic concentrations, resistant starch content and glycemic properties of Russet Burbank and Shepody potatoes. Product forms included French fries, shredded (hash browns) and diced (home fries) produced through commercial processing as well as parallel in-home techniques. Commercial products had significantly higher concentrations of resistant starch (p < 0.05, 1.48-6.57 vs. 1.23-2.22 g per 100 fresh weight) and resistant starch/total starch ratio (5.42-18.3% vs. 3.58-7.62%) compared to freshly prepared counterparts, while statistically lower total caffeoylquinic acid content (2.94-10.9 vs. 11.5-25.2 g per 100 fresh weight). Glucose release and intestinal transport assessed using an in vitro digestion/Caco-2 cell monolayers model demonstrated a reduction in d7-glucose intestinal transport from commercially processed products relative to fresh prepared counterparts (p < 0.05, 31.3-61.2% vs. 79.3-110% at 60 min). Commercial Russet Burbank potato products including French fries, home fries and hash browns were then selected for clinical assessment of glycemic response and appetite rating by 23 participants (11 male and 12 female). The three products presented a subtle but discernable ascending trend (French fry ≥ home fry ≥ hash browns) for incremental area under the curve (IAUC, 95.2 ± 12 vs. 105 ± 10 vs. 107 ± 14 mM min, p < 0.05) at 2 h post breakfast and for appetite rating (45.2 ± 6.3 vs. 52.4 ± 4.1 vs. 57.7 ± 7.2 for hunger) at 4 h post breakfast with no significant difference from the control (whole wheat pancake). These results suggest that potato phenolics have only a modest influence on acute glycemic responses.
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4.
Modeling Glucose Transport From Systemic Circulation to Sweat.
La Count, TD, Jajack, A, Heikenfeld, J, Kasting, GB
Journal of pharmaceutical sciences. 2019;(1):364-371
Abstract
Sweat sensing may provide a noninvasive means of estimating blood biomarker levels if a number of technological hurdles can be overcome. This report describes progress on a physiologically based transport model relating sweat glucose and key electrolyte concentrations to those in blood. Iontophoretically stimulated sweat glucose and fasted blood glucose were simultaneously measured in 2 healthy human subjects. Sweat glucose was measured with a novel, prototype skin sweat collection/analysis system and blood glucose with a commercial fingerstick glucometer. These data, in combination with data from 3 published studies, were used to calibrate a dynamic mathematical model for glucose transport and uptake in human skin, followed by extraction into sweat. Model simulations revealed that experimental and literature sweat glucose values were well represented under varying physiologic conditions. The glucose model, calibrated under a variety of experimental conditions including electrical enhancement, revealed a 10 min blood-to-sweat lag time and a sweat/blood glucose level ranging from 0.001 to 0.02, depending on the sweat rate. These values are consistent with those reported in the literature. The developed model satisfactorily described the sweat-to-blood relationship for glucose concentrations measured under different conditions in 4 human studies including the present pilot study. The algorithm may be used to facilitate sweat biosensor development.
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Spatiotemporal pattern of glucose in a microfluidic device depend on the porosity and permeability of the medium: A finite element study.
Bonifácio, ED, González-Torres, LA, Meireles, AB, Guimarães, MV, Araujo, CA
Computer methods and programs in biomedicine. 2019;:105039
Abstract
BACKGROUND Glucose plays an important role as a source of nutrients and influence cellular processes such as differentiation, proliferation and migration. In vitro models based on microfluidic devices represent an alternative to study several biological processes in a more reproducible and controllable method compared to in vivo models. Glucose concentration across a microfluidic chip and its behavior in experimental conditions is not completely understood. OBJECTIVE This paper investigated the spatiotemporal distribution of glucose across the hydrogel inside a microfluidic chip. The influence of different parameters, boundary and initial conditions of experiments on glucose concentration was studied. METHODS A finite element model using a two dimensional geometry was developed. With this model, patterns of glucose concentration were investigated for different combinations of flow rate of culture medium, permeability and porosity of the medium. Patterns were also studied for two hydrogels made of collagen type I and fibrin with different initial and boundary conditions for pressure and glucose concentration. RESULTS Porosity influenced significantly on the chemical gradients generated when interstitial fluid flow was null or neglectable. A difference in concentration lower than 15% was obtained at the input of microchamber and after 90 min, when porosity changed from 0.5 to 0.99. In addition, no significant effects of modifications in permeability were observed. Regarding the collagen and fibrin matrices, in the presence of a pressure gradient of 40 Pa, the permeability significantly influenced on the concentration gradients generated. CONCLUSIONS Porosity influences importantly on patterns when diffusion is the main transport mechanism. Permeability is the most influencing parameter when a fluid flow is present. Common insertion rates of culture medium does not significantly modify the patterns of glucose inside the chips. Thus, new experiments must consider the impact of such parameters on the distribution and the time span that nutrients occupy the medium. To better contribute with experimental trials, other studies involving cell-cell and cell-extracellular matrix interactions, and different chip geometries should be developed. The results of the present work could assist to develop specific systems for experimentation, to design new experiments and to improve the analysis of the obtained results.
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6.
Augmentation of Glucotoxicity, Oxidative Stress, Apoptosis and Mitochondrial Dysfunction in HepG2 Cells by Palmitic Acid.
Alnahdi, A, John, A, Raza, H
Nutrients. 2019;(9)
Abstract
Hyperglycemia and hyperlipidemia are the hallmarks of diabetes and obesity. Experimental and epidemiological studies have suggested that dietary management and caloric restriction are beneficial in reducing the complications of diabesity. Studies have suggested that increased availability of energy metabolites like glucose and saturated fatty acids induces metabolic, oxidative, and mitochondrial stress, accompanied by inflammation that may lead to chronic complications in diabetes. In the present study, we used human hepatoma HepG2 cells to investigate the effects of high glucose (25 mM) and high palmitic acid (up to 0.3 mM) on metabolic-, inflammatory-, and redox-stress-associated alterations in these cells. Our results showed increased lipid, protein, and DNA damage, leading to caspase-dependent apoptosis and mitochondrial dysfunction. Glucolipotoxicity increased ROS production and redox stress appeared to alter mitochondrial membrane potential and bioenergetics. Our results also demonstrate the enhanced ability of cytochrome P450s-dependent drug metabolism and antioxidant adaptation in HepG2 cells treated with palmitic acid, which was further augmented with high glucose. Altered NF-kB/AMPK/mTOR-dependent cell signaling and inflammatory (IL6/TNF-α) responses were also observed. Our results suggest that the presence of high-energy metabolites enhances apoptosis while suppressing autophagy by inducing inflammatory and oxidative stress responses that may be responsible for alterations in cell signaling and metabolism.
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7.
Postprandial Aminogenic Insulin and Glucagon Secretion Can Stimulate Glucose Flux in Humans.
Ang, T, Bruce, CR, Kowalski, GM
Diabetes. 2019;(5):939-946
Abstract
Insulin and glucagon exert opposing actions on glucose metabolism, and their secretion is classically viewed as being inversely regulated. This is, however, context specific as protein ingestion concomitantly stimulates euglycemic insulin and glucagon secretion. It remains enigmatic how euglycemia is preserved under these conditions. Accordingly, we examined the systems-level mechanisms governing such endocrine control of glucose homeostasis. Eight healthy participants completed a water (control) and multidose whey protein ingestion trial designed to augment the protein-induced endocrine response. Glucose kinetics were measured using stable isotope tracer methodology. Protein ingestion induced marked hyperaminoacidemia, hyperinsulinemia (approximately sixfold basal), and unprecedented hyperglucagonemia (approximately eightfold basal) while suppressing free fatty acids. Both glucose disposal (Rd) and endogenous glucose production (EGP) increased by ∼25%, thereby maintaining euglycemia. This demonstrates 1) that protein ingestion can stimulate glucose Rd and EGP, 2) that postprandial inhibition of adipose lipolysis does not suppress EGP, and 3) that physiological hyperglucagonemia can override the hepatic actions of insulin, rendering the liver unresponsive to insulin-mediated EGP suppression. Finally, we argue that glucagon is a bona fide postprandial hormone that evolved to concurrently and synergistically work with insulin to regulate glucose, amino acid, and nitrogen metabolism. These findings may have implications for glucagon receptor antagonist or agonist-based therapies.
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8.
Hepatitis C Virus Downregulates Core Subunits of Oxidative Phosphorylation, Reminiscent of the Warburg Effect in Cancer Cells.
Gerresheim, GK, Roeb, E, Michel, AM, Niepmann, M
Cells. 2019;(11)
Abstract
Hepatitis C Virus (HCV) mainly infects liver hepatocytes and replicates its single-stranded plus strand RNA genome exclusively in the cytoplasm. Viral proteins and RNA interfere with the host cell immune response, allowing the virus to continue replication. Therefore, in about 70% of cases, the viral infection cannot be cleared by the immune system, but a chronic infection is established, often resulting in liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Induction of cancer in the host cells can be regarded to provide further advantages for ongoing virus replication. One adaptation in cancer cells is the enhancement of cellular carbohydrate flux in glycolysis with a reduction of the activity of the citric acid cycle and aerobic oxidative phosphorylation. To this end, HCV downregulates the expression of mitochondrial oxidative phosphorylation complex core subunits quite early after infection. This so-called aerobic glycolysis is known as the "Warburg Effect" and serves to provide more anabolic metabolites upstream of the citric acid cycle, such as amino acids, pentoses and NADPH for cancer cell growth. In addition, HCV deregulates signaling pathways like those of TNF-β and MAPK by direct and indirect mechanisms, which can lead to fibrosis and HCC.
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9.
Effect of purslane on blood lipids and glucose: A systematic review and meta-analysis of randomized controlled trials.
Hadi, A, Pourmasoumi, M, Najafgholizadeh, A, Kafeshani, M, Sahebkar, A
Phytotherapy research : PTR. 2019;(1):3-12
Abstract
Despite a history of purslane usage as a herbal treatment for dyslipidemia and hyperglycemia management, existing evidence from clinical trials is controversial. The aim for the current study was to evaluate the efficacy of purslane supplementation on lipid parameters and glycemic status in adult populations. A systematic review was conducted in PubMed, Scopus, ISI Web of Science, and Google Scholar up to January 15, 2018, searching for randomized controlled trials that assessed the impact of purslane on fasting blood glucose (FBG), triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Based on the detected heterogeneity between studies, a random- or fixed-effect model was applied in the meta-analysis. The findings from six randomized controlled trials, comprising 352 participants, indicated that purslane can reduce FBG (-4.54 mg/dl, 95% CI [-7.54, -1.53]; I2 = 0.53%) and triglycerides (-19.16 mg/dl, 95% CI [-38.17, -0.15]; I2 = 0%) levels. Changes in TC, LDL-C, and HDL-C concentrations did not reach a statistically significant level. Subgroup analysis showed a favorable effects of purslane on FBG, triglycerides, TC, and LDL-C in a subset of studies in which purslane was administered >1.5 g/day. Categorization based on gender showed that purslane was more effective in improving FBG, TC and LDL-C in females compared with males. This systematic review and meta-analysis suggested that the purslane might be effective on the improvement of blood lipid and glucose levels. Further robust studies with sufficient durations and dosages of supplementation are needed to confirm these results.
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10.
Glucose- and Lipid-Related Biomarkers Are Affected in Healthy Obese or Hyperglycemic Adults Consuming a Whole-Grain Pasta Enriched in Prebiotics and Probiotics: A 12-Week Randomized Controlled Trial.
Angelino, D, Martina, A, Rosi, A, Veronesi, L, Antonini, M, Mennella, I, Vitaglione, P, Grioni, S, Brighenti, F, Zavaroni, I, et al
The Journal of nutrition. 2019;(10):1714-1723
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Abstract
BACKGROUND Synbiotic foods, which combine the action of prebiotics and probiotics along the gastrointestinal tract, can affect inflammatory and glucose-related markers. OBJECTIVE The aim of this study was to investigate the effects on inflammatory and glycemia-related markers of a whole-grain pasta containing barley β-glucans and Bacillus coagulans BC30, 6086 in healthy overweight or obese volunteers. METHODS A single-blind, parallel, randomized, placebo-controlled dietary intervention study was carried out. Forty-one healthy sedentary overweight (body mass index [BMI] 25-29.9 kg/m2) and obese (BMI ≥30) volunteers, aged 30-65 y and low consumers of fruit and vegetables, ate 1 serving/d of whole-grain control (CTR) or innovative (INN) pasta for 12 wk and maintained their habitual diets. Biological samples were collected at baseline and every 4 wk for primary (plasma high-sensitivity C-reactive protein [hs-CRP] and fasting plasma lipid profile) and secondary outcomes (glycemia-related markers, blood pressure, fecal microbiota composition, and body weight). Between (CTR compared with INN) and within (among weeks) group differences were tested for the whole population and for subgroups stratified by baseline values of BMI (≥30) and glycemia (≥100 mg/dL). RESULTS INN or CTR pasta consumption had no effect on primary and secondary outcomes over time, except for a significant increase in plasma γ-glutamyltransferase (GGT) after 12 wk of CTR pasta consumption. Comparisons between intervention groups revealed differences only at 12 wk: plasma GGT was higher in the CTR group; plasma hs-CRP, plasma LDL/HDL cholesterol ratio, and Bifidobacterium spp. were lower in the INN subgroup of obese volunteers; plasma resistin was lower and Faecalibacterium prausnitzii abundance was higher in the INN subgroup of hyperglycemic volunteers. CONCLUSIONS A daily serving of a synbiotic whole-grain pasta had limited effects on primary and secondary outcomes in the entire group of volunteers but affected glycemia- and lipid-related markers and resistin in a subgroup of healthy obese or hyperglycemic volunteers. This trial was registered at clinicaltrials.gov as NCT02236533.