-
1.
Electrophysiological properties of human beta-cell lines EndoC-βH1 and -βH2 conform with human beta-cells.
Hastoy, B, Godazgar, M, Clark, A, Nylander, V, Spiliotis, I, van de Bunt, M, Chibalina, MV, Barrett, A, Burrows, C, Tarasov, AI, et al
Scientific reports. 2018;(1):16994
Abstract
Limited access to human islets has prompted the development of human beta cell models. The human beta cell lines EndoC-βH1 and EndoC-βH2 are increasingly used by the research community. However, little is known of their electrophysiological and secretory properties. Here, we monitored parameters that constitute the glucose-triggering pathway of insulin release. Both cell lines respond to glucose (6 and 20 mM) with 2- to 3-fold stimulation of insulin secretion which correlated with an elevation of [Ca2+]i, membrane depolarisation and increased action potential firing. Similar to human primary beta cells, KATP channel activity is low at 1 mM glucose and is further reduced upon increasing glucose concentration; an effect that was mimicked by the KATP channel blocker tolbutamide. The upstroke of the action potentials reflects the activation of Ca2+ channels with some small contribution of TTX-sensitive Na+ channels. The repolarisation involves activation of voltage-gated Kv2.2 channels and large-conductance Ca2+-activated K+ channels. Exocytosis presented a similar kinetics to human primary beta cells. The ultrastructure of these cells shows insulin vesicles composed of an electron-dense core surrounded by a thin clear halo. We conclude that the EndoC-βH1 and -βH2 cells share many features of primary human β-cells and thus represent a useful experimental model.
-
2.
The effect of drinking water pH on the human gut microbiota and glucose regulation: results of a randomized controlled cross-over intervention.
Hansen, TH, Thomassen, MT, Madsen, ML, Kern, T, Bak, EG, Kashani, A, Allin, KH, Hansen, T, Pedersen, O
Scientific reports. 2018;(1):16626
Abstract
Studies in rodent models have shown that alterations in drinking water pH affect both the composition of the gut microbiota and host glucose regulation. To explore a potential impact of electrochemically reduced alkaline (pH ≈ 9) versus neutral (pH ≈ 7) drinking water (2 L/day) on human intestinal microbiota and host glucose metabolism we conducted a randomized, non-blinded, cross-over study (two 2-week intervention periods, separated by a 3-week wash-out) in 29 healthy, non-smoking Danish men, aged 18 to 35 years, with a body mass index between 20.0 to 27.0 kg m-2. Volunteers were ineligible if they had previously had abdominal surgery, had not been weight stabile for at least two months, had received antibiotic treatment within 2 months, or had a habitual consumption of caloric or artificially sweetened beverages in excess of 1 L/week or an average intake of alcohol in excess of 7 units/week. Microbial DNA was extracted from faecal samples collected at four time points, before and after each intervention, and subjected to 16S rRNA gene amplicon sequencing (Illumina MiSeq, V4 region). Glycaemic regulation was evaluated by means of an oral glucose tolerance test.No differential effect of alkaline versus neutral drinking water was observed for the primary outcome, overall gut microbiota diversity as represented by Shannon's index. Similarly, neither a differential effect on microbiota richness or community structure was observed. Nor did we observe a differential effect on the abundance of individual operational taxonomic units (OTUs) or genera. However, analyses of within period effects revealed a significant (false discovery rate ≤5%) increase in the relative abundance of 9 OTUs assigned to order Clostridiales, family Ruminococcaceae, genus Bacteroides, and species Prevotella copri, indicating a potential effect of quantitative or qualitative changes in habitual drinking habits. An increase in the concentration of plasma glucose at 30 minutes and the incremental area under the curve of plasma glucose from 0 30 and 0 120 minutes, respectively, was observed when comparing the alkaline to the neutral intervention. However, results did not withstand correction for multiplicity. In contrast to what has been reported in rodents, a change in drinking water pH had no impact on the composition of the gut microbiota or glucose regulation in young male adults. The study is registered at www.clinicaltrials.gov (NCT02917616).
-
3.
Daily Consumption of Chocolate Rich in Flavonoids Decreases Cellular Genotoxicity and Improves Biochemical Parameters of Lipid and Glucose Metabolism.
Leyva-Soto, A, Chavez-Santoscoy, RA, Lara-Jacobo, LR, Chavez-Santoscoy, AV, Gonzalez-Cobian, LN
Molecules (Basel, Switzerland). 2018;(9)
Abstract
In recent years, the incidence of atherosclerotic cardiovascular disease, obesity, and diabetes has increased largely worldwide. In the present work, we evaluated the genoprotective effect of the consumption of flavonoids-rich chocolate on 84 young volunteers. Biochemical indicators related to the prevention and treatment of cardiovascular risk and metabolic syndrome were also determined. A randomized, placebo-controlled, double-blind study was performed in the Autonomous University of Baja California. The treatments comprised the daily consumption of either 2 g of dark chocolate containing 70% cocoa, or 2 g of milk chocolate, for 6 months. The total amount of phenolic compounds and flavonoids was determined in both types of chocolate. Anthropometrical and Biochemical parameters were recorded prior to and after the study. The evaluation of the genotoxicity in buccal epithelial cells was performed throughout the duration of the study. Flavonoids from cocoa in dark chocolate significantly prevented DNA damage, and improved the nucleus integrity of cells. This effect could be related to the antioxidant capacity of the dark chocolate that decreased cellular stress. Biochemical parameters (total cholesterol, triglycerides, and LDL-cholesterol level in blood) and anthropometrical parameters (waist circumference) were improved after six months of daily intake of 2 g of dark chocolate with a 70% of cocoa.
-
4.
Fat Mass and Obesity Associated (FTO) Gene and Hepatic Glucose and Lipid Metabolism.
Mizuno, TM
Nutrients. 2018;(11)
Abstract
Common genetic variants of the fat mass and obesity associated (FTO) gene are strongly associated with obesity and type 2 diabetes. FTO is ubiquitously expressed. Earlier studies have focused on the role of hypothalamic FTO in the regulation of metabolism. However, recent studies suggest that expression of hepatic FTO is regulated by metabolic signals, such as nutrients and hormones, and altered FTO levels in the liver affect glucose and lipid metabolism. This review outlines recent findings on hepatic FTO in the regulation of metabolism, with particular focus on hepatic glucose and lipid metabolism. It is proposed that abnormal activity of hepatic signaling pathways involving FTO links metabolic impairments such as obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Therefore, a better understanding of these pathways may lead to therapeutic approaches to treat these metabolic diseases by targeting hepatic FTO. The overall goal of this review is to place FTO within the context of hepatic regulation of metabolism.
-
5.
Non-coding RNAs in the reprogramming of glucose metabolism in cancer.
Shankaraiah, RC, Veronese, A, Sabbioni, S, Negrini, M
Cancer letters. 2018;:167-174
Abstract
Proliferating cancer cells reprogram their metabolic circuitry to thrive in an environment deficient in nutrients and oxygen. Cancer cells exhibit a higher rate of glucose metabolism than normal somatic cells, which is achieved by switching from oxidative phosphorylation to aerobic glycolysis to meet the energy and metabolites demands of tumour progression. This phenomenon, which is known as the Warburg effect, has generated renewed interest in the process of glucose metabolism reprogramming in cancer cells. Several regulatory pathways along with glycolytic enzymes are responsible for the emergence of glycolytic dependence. Non-coding (nc)RNAs are a class of functional RNA molecules that are not translated into proteins but regulate target gene expression. NcRNAs have been shown to be involved in various biological processes, including glucose metabolism. In this review, we describe the regulatory role of ncRNAs-specifically, microRNAs and long ncRNAs-in the glycolytic switch and propose that ncRNA-based therapeutics can be used to inhibit the process of glucose metabolism reprogramming in cancer cells.
-
6.
Emerging Concepts in Brain Glucose Metabolic Functions: From Glucose Sensing to How the Sweet Taste of Glucose Regulates Its Own Metabolism in Astrocytes and Neurons.
Welcome, MO, Mastorakis, NE
Neuromolecular medicine. 2018;(3):281-300
Abstract
The astrocyte-neuron lactate shunt (ANLS) hypothesis is the most widely accepted model of brain glucose metabolism. However, over the past decades, research has shown that neuronal and astrocyte plasma membrane receptors, in particular, GLUT2, Kir6.2 subunit of the potassium ATP-channel, SGLT-3 acting as glucosensors, play a pivotal role in brain glucose metabolism. Although both ANLS hypothesis and glucosensor model substantially improved our understanding of brain glucose metabolism, the latter appears to be gaining more attention in the scientific community as the former could not account for new research data indicating that hypothalamic and brainstem neurons may not require astrocyte-derived lactate for energy. More recently, emerging evidences suggest a crucial role of sweet taste receptors in brain glucose metabolism. Furthermore, a couple of intracellular molecules acting as glucosensors have been identified in central astrocytes and neurons. This review integrates new data on the mechanisms of brain glucose sensing and metabolism. The role of the glucosensors including the sweet taste T1R2 + T1R3-mediated brain glucose-sensing and metabolism in brain glucose metabolic disorders is discussed. Possible role of glucose sensors (GLUT2, K-ATPKir6.2, SGLT3, T1R2 + T1R3) in brain diseases involving metabolic dysfunctions and the therapeutic significance in targeting central glucosensors for the treatment of these brain diseases are also discussed.
-
7.
Effects of Coffee and Tea Consumption on Glucose Metabolism: A Systematic Review and Network Meta-Analysis.
Kondo, Y, Goto, A, Noma, H, Iso, H, Hayashi, K, Noda, M
Nutrients. 2018;(1)
Abstract
Prospective cohort studies have described an association between coffee or tea consumption and the risk of developing diabetes. However, whether coffee or tea improves glucose metabolism remains uncertain. We investigated the effect of coffee and tea on glucose metabolism by conducting a systematic review and meta-analysis of randomized controlled trials. Electronic databases were searched for articles published up 19 February 2017. The primary endpoint was the mean difference in post-intervention fasting blood glucose (FBG) levels between the groups. Of 892 citations screened, 27 studies (1898 participants) were included in our meta-analysis. A network meta-analysis suggested that green tea, but not caffeinated/decaffeinated coffee or black tea, may reduce FBG levels, compared with placebo/water (-2.10 mg/dL; 95% confidence interval (CI), -3.96 to -0.24 mg/dL; p = 0.03; moderate quality of evidence). In a subgroup analysis, the effect of green tea on FBG levels was statistically significant only in studies with a mean age of < 55-years-old or Asian-based studies. The oolong tea group also showed a significant decrease in FBG, but the quality of evidence was very low. In conclusion, green tea consumption might decrease FBG levels, especially in < 55-year-olds or Asian-based populations.
-
8.
The Influence of Pre-Exercise Glucose versus Fructose Ingestion on Subsequent Postprandial Lipemia.
Yang, TJ, Chiu, CH, Tseng, MH, Chang, CK, Wu, CL
Nutrients. 2018;(2)
Abstract
Ingestion of low glycemic index (LGI) carbohydrate (CHO) before exercise induced less insulin response and higher fat oxidation than that of high GI (HGI) CHO during subsequent exercise. However, the effect on the subsequent postprandial lipid profile is still unclear. Therefore, the aim of this study was to investigate ingestion of CHO drinks with different GI using fructose and glucose before endurance exercise on the subsequent postprandial lipid profile. Eight healthy active males completed two experimental trials in randomized double-blind cross-over design. All participants ingested 500 mL CHO (75 g) solution either fructose (F) or glucose (G) before running on the treadmill at 60% VO₂max for 1 h. Participants were asked to take an oral fat tolerance test (OFTT) immediately after the exercise. Blood samples were obtained for plasma and serum analysis. The F trial was significantly lower than the G trial in TG total area under the curve (AUC; 9.97 ± 3.64 vs. 10.91 ± 3.56 mmol × 6 h/L; p = 0.033) and incremental AUC (6.57 ± 2.46 vs. 7.14 ± 2.64 mmol/L × 6 h, p = 0.004). The current data suggested that a pre-exercise fructose drink showed a lower postprandial lipemia than a glucose drink after the subsequent high-fat meal.
-
9.
Impaired brain energy gain upon a glucose load in obesity.
Wardzinski, EK, Kistenmacher, A, Melchert, UH, Jauch-Chara, K, Oltmanns, KM
Metabolism: clinical and experimental. 2018;:90-96
Abstract
BACKGROUND There is evidence that the brain's energy status is lowered in obesity despite of chronic hypercaloric nutrition. The underlying mechanisms are unknown. We hypothesized that the brain of obese people does not appropriately generate energy in response to a hypercaloric supply. METHODS Glucose was intravenously infused in 17 normal weights and 13 obese participants until blood glucose concentrations reached the postprandial levels of 7 mmol/L and 10 mmol/L. Changes in cerebral adenosine triphosphate (ATP) and phosphocreatine (PCr) content were measured by 31phosphorus magnetic resonance spectroscopy and stress hormonal measures regulating glucose homeostasis were monitored. Because vitamin C is crucial for a proper neuronal energy synthesis we determined circulating concentrations during the experimental testing. RESULTS Cerebral high-energy phosphates were increased at blood glucose levels of 7 mmol/L in normal weights, which was completely missing in the obese. Brain energy content moderately raised only at blood glucose levels of 10 mmol/L in obese participants. Vitamin C concentrations generally correlated with the brain energy content at blood glucose concentrations of 7 mmol/L. CONCLUSIONS Our data demonstrate an inefficient cerebral energy gain upon a glucose load in obese men, which may result from a dysfunctional glucose transport across the blood-brain barrier or a downregulated energy synthesis in mitochondrial oxidation processes. Our finding offers an explanation for the chronic neuroenergetic deficiency and respectively missing satiety perception in obesity.
-
10.
Effect of Prolonged Fasting Duration on 50 Gram Oral Glucose Challenge Test in the Diagnosis of Gestational Diabetes Mellitus.
Hancerliogullari, N, Celik, HK, Karakaya, BK, Tokmak, A, Tasci, Y, Erkaya, S, Engin-Ustun, Y, Ozgu-Erdinc, AS
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2018;(9):671-674
Abstract
The aim of this study was to investigate the association between fasting duration before screening with 50 g glucose challenge test (GCT) and the test outcome. For this cross-sectional study, we enrolled 508 low-risk pregnant women who underwent 50 g GCT between the 24 and 28 weeks of gestation. We excluded women with pregestational diabetes, multiple gestations or a history of gestational diabetes mellitus (GDM), and macrosomia. We evaluated fasting durations, GCT results, and demographic features. A significant positive correlation was found between fasting duration and 50 g GCT values (r=0.122; p=0.006), and the best cut-off value was found to be 6.5 h, with 85.85% sensitivity and 38.61% specificity (relative risk, 2.73; 95% CI, 1.893-3.936; p<0.0001). Further, we divided the patients into two groups: study (fasting, <6.5 h; n=146) and control (fasting,>6.5 h; n=362) groups. Notably, the mean glucose levels, number of patients with GCT>140 mg/dl, and rates of unnecessary 100 g loadings were significantly higher in the study group. We found no significant differences between the groups in terms of the fasting plasma glucose levels and GDM prevalence. According to our findings, fasting duration of>6.5 h resulted in 2.7 times more unnecessary 100 g glucose tolerance tests (GTT). We recommend that patients having fasted for>6.5 h receive a one-step 75 g GTT after completing 8-h fasting.